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301 Cards in this Set
- Front
- Back
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Which pituitary hormones come from similar lineages?
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What regulates hypothalamic factors?
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Circadian rhythm regulates ANS and hypothalamus
*The Higher Power |
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What is this showing?
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graph of various hormones
* don't come back down to normal like they should when your sleep deprived = increase BP, increase blood glucose- why you grab junk food in these cases * day time sleeping throws it off as well *GH at beginning of sleep - need sleep to grow |
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What is this showing?
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top - untreated sleep apnea = GH levels aren't turned on like the should be
bottom- sleep apnea with CPac - now the GH levels go back to normal |
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What are the two hormones that affect GH release from the anterior pituitary?
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GHRH (Growth hormone- releasing hormone) has a positive effect - stimulates both synthesis and secretion
SS (Somatostatin) - peptide that inhibits GH release - released in response to hormonal, neurologic, and nutritional cues |
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What is Ghrelin?
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peptide hormone that is secreted from the stomach and binds to receptors on somatotrophs to stimulate secretion of growth hormone
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How is GH controlled?
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*Ghrelin has a positive effect on GH release
*GH positively affects its conversion to IGF-1 within the liver *IGF has a negative feedback on pituitary release of GH *IGF also stimulates SS, which decreases GH release *GH also inhibits GHRH secretion |
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What is the release pattern for GH?
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pulsatile pattern of release
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Are basal concentrations of GH high or low?
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Very low
see highest concentrations shortly after the onset of deep sleep |
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Direct effect- GH binding to its receptor (Fat cells have a GH-R)
*stimulates adipocytes to break down triglycerides and suppresses their ability to take up lipids indirect- mediated by IGF-1 (increase in long bone length) |
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What does a manual muscle test of (2) indicate?
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Poor (P): Part moves through complete range of motion with gravity decreased
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GH's effect on protein metabolism?
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GH stimulates protein anabolism
- leading to increase in aa uptake |
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GH's effect on fat metabolism?
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GH enhances the utilization of fat by stimulating triglyceride breakdown and oxidation in adipocytes
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GH's effect on carbohydrate metabolism?
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GH maintins blood glucose levels within a normal range
* suppress the abilities of insulin to stimulate uptake of glucose * yet increase GH stimulates insulin secretion = hyperinsulinemia |
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GH deficiency?
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Growth retardation or dwarfism
* heritable or acquired |
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GH excess (2 disorders)
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1) Gigantism - excessive GH from childhood (tumor of somatotrophs)
2) Acromegaly - excessive secretion of GH as an adult- overgrowth of bone and connective tissue = coarse features and glucose intolerance |
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What else is thyroid stimulating hormone called? What cells is it secreted from?
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Thyrotropin
Secreted from thyrotrophs |
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Which pituitary hormones have alpha sub-unit homology?
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TSH, FSH and LH
each has a unique Beta-subunit - provides receptor specificity |
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What else is thyroid stimulating hormone called? What cells is it secreted from?
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Thyrotropin
Secreted from thyrotrophs |
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Which pituitary hormones have alpha sub-unit homology?
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TSH, FSH and LH
each has a unique Beta-subunit - provides receptor specificity |
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Thyroid releasing hormone is secreted by hypothalamic neurons into hypothalaic hypophyseal portal blood
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Secondary Hypothyroidism
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absence of TSH
low levels of thyroid hormone and inappropriately low or normal levels of TSH |
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Primary Hypothyroidism
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High TSH levels
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TSHomas
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very rare tumors in the pituitary gland - secrete TSH
- stimulate the thyroid gland to produce thyroid hormone = hyperthyroidism |
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ACTH= corticotropin
CRH- corticotropin-releasing hormone released in response to stress |
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What is the large precursor protein that ACTH is made from? What else does it make?
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*Lipotropin - weak lipolytic effects precursor to Beta-endorphin
*Beta-endorphin & Met-enkephalin - Opioid peptides with pain alleviation *Melanocyte-stimulating hormone (MSH): control melanin |
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What does ACTH do?
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stimulates the adrenal cortex
stimulates secretion of glucocorticoids (cortisol) - little control over aldosterone secretion |
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Excessive ACTH leads to what?
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ACTH secreting pituitary adenoma or hperplasia - overstimulation of the adrenal gland producing excess cortisol
* Hypercortisolemia ensues |
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What does excess cortisol lead to?
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hypertension, impaired glucose tolerance, muscle wasting, easy bruising, immune dysfunction and psychiatric disturbances
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Insufficient ACTH?
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inadequate cortisol secretion from the adrenal glands
*hyptotension and hypoglycemia |
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What is this showing?
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The normal release of ACTH and its stimulation of cortisol release
* about 10 spikes * during sleep both levels drop |
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What is this graph showing?
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CRF- corticoreleasing factor
inject CRF - ACTH increase 4x- But if you turn off ACTH with (glucocorticoids then CRF has no effect |
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What cells secrete prolactin?
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Lactotrophs in the anterior pituitary
*immune cells, brain, and decidua or uterus also secrete this hormone |
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What is prolactin responsible for?
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milk production
mammary gland development *induces lobuloalveolar growth - alveoli are what secrete milk * lactogenosis = milk production (+cortisol + insulin = for milk genes) |
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What is interesting and different about prolactin secretion?
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It is controlled by a "brake" mechanism through dopamine
* hypothalamus tonically suppresses prolactin secretion |
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What are the stimulatory factors for prolactin?
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nipple stimulation, estrogens, and any drug that inhibits dopamine will increase prolactin secretion
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Dopamine is a prolactin inhibiting factor
stimulatory factors (drugs and nipple stimulation) Estrogens - positive control in late pregnancy |
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What is Hyperprolactinemia?
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Excessive secretion of prolactin
due to a prolactin secreting tumor *manifestations include: 1) amenorrhea - lack of period 2) galactorrhea - excessive or spontaneous secretion of milk * men with this condition - hypogonadism, large secretions of sperm but infertile |
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What are the two gonadotropins?
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LH and FSH - stimulate the gonads
secreted from cells called = gonadotrophs *essential for reproduction |
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Regulation of Gonadotropin?
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*GnRH peptide synthesized and secreted from hypothalamic neurons and binds to receptors on gonadotrophs
* LH and FSH in turn stimulate sex steroids * sex steroids have a negative feedback on GnRH and the gonatrophs **pulsatile secretion |
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What are the two additional hormones the gonads secrete?
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inhibin and activin
* selectively inhibit and activate FSh secretion from the pituitary |
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What is the effect of LH in men?
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LH binds to receptors on leydig cells - stimulates the secretion of testosterone
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What is the effect of LH in women?
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LH binds to theca cells - secrete testosterone - converted to estrogen by adjacent granulosa cells
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What is the effect of FSH in men?
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supports Sertoli cells
importnat for sperm maturation |
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What is the effect of FSH in women?
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maturation of ovarian follicle
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What occurs in hypogonadism?
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diminished secretion of LH and FSH
males- failure to reproduce normal number of living sperm women- cessation of reproductive cycles |
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What is the effect of LH in men?
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LH binds to receptors on leydig cells - stimulates the secretion of testosterone
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What is the effect of LH in women?
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LH binds to theca cells - secrete testosterone - converted to estrogen by adjacent granulosa cells
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What is the effect of FSH in men?
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supports Sertoli cells
importnat for sperm maturation |
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What is the effect of FSH in women?
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maturation of ovarian follicle
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What occurs in hypogonadism?
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diminished secretion of LH and FSH
males- failure to reproduce normal number of living sperm women- cessation of reproductive cycles |
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What does elevated gonadotropins usually indicate?
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lack of negative feedback of steroid hormones
*removal of gonads leads to persistent elevation in LH and FSH |
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What is one widely used strategy for contraception?
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interfering with LH secretion - inhibiting the LH surge that induces ovulation
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Other than inhibiting the LH surge, what is another contraceptive?
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Blocking the release of GnRH, this blocks the receptor in both males and females
*hasn't really been utilized |
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What are the two hormones secreted from the posterior pituitary?
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ADH
Oxytocin |
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with the administration of TRH you see an excessive spike in TSH
*uncontrollable hyperthyroid - very skinny |
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What triggers ADH release?
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increased osmolality
decreased pressure or volume *osmoreceptors stimulate ADH and thirst but ADH has a much lower threshold |
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What is another name for ADH?
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vasopressin
*hormone is packaged into secretory vesicles within a carrier protein = neurophysin |
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What is diabetes insipidus? Describe the two different forms?
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Central - posterior pituitary has a deficiency in secretion of ADH
Nephrogenic- the kidney is unable to respond to ADH *Major signs: excessive urine productions and severe thirst |
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Where is Oxytocin synthesized and secreted?
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Synthesized in hypothalamic neurons and transported down axons of the posterior pituitary for secretion from there into the blood.
**also packaged into granules and secreted with the carrier protein, neurophysins |
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What can inhibit oxytocin release?
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stress - oxytocin is inhibited by catecholamines which are released from adrenal gland in response to many types of stress
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What modulates the production and response of oxytocin?
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productions and response to oxytocin is modulated by circulating levels of sex steroids
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What are the physiological effects of oxytocin?
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1) stimulation of milk ejection
2) stimulation of uterine smooth muscle contraction at birth 3) establishment of maternal behavior |
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What are the hormone secretion level differences between normal individuals and someone with hypopituitarism?
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What are the 4 classes of hormones that are secreted from the adrenal gland?
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1) aldosterone
2) cortisol 3) androgens 4) catecholamines |
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What is the anatomy of the adrenal gland?
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Why is the blood supply to the left adrenal gland harder to access?
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artery underneath the left suprarenal vein
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Describe the zones of the adrenal gland?
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What is the pathway to producing the products of the adrenal cortex?
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What occurs in the adrenal gland when one encounters a perceived stimulus?
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Metabolic and Hemodynamic effects of glucocorticoids?
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Glucocorticoids effects on immune system and CNS?
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What is the component of Cushing's disease?
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increase in glucocortecoids
-severe bone loss |
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In the situation where cortisol is in excess in the blood why don't you want to measure directly in the blood
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1) diurnal pattern of excretion
2) cortisol binds to binding globulins in the blood |
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Where should you measure cortisol levels?
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the free cortisol in urine from a 24 hour urine sample
* can also measure it in salvia but it is also affected by diurnal variation as well (but midnight salivary cortisol is almost as good as 24 hr. urine) |
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Why would ACTH be un detectable in a patient with excess cortisol levels?
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Because cortisol has a negative feedback mechanism on ACTH
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Why was the patient with high levels of cortisol red in the face?
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Because high levels of cortisol stimulates BM to produce more RBC and WBC and the high levels also lead to capillary fragility
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explain the negative feedback mechanism of the adrenal gland?
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What is Addison's disease?
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impaired adrenal function
*Primary adrenal insufficiency |
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what are the laboratory findings with Addison's disease?
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Low Na- more excreted in the urine
High K Low HCO3 and High BUN *Plasma renin and ACTH are also increased *losing Na will increase H2O excretion as well - leading to weight loss |
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How does one determine if Addison's disease is the diagnosis?
What will the test results look like if this is the diagnosis? |
Testing is performed by injecting cosyntropin 5 to 250 µg IV. Normal preinjection plasma cortisol ranges from 5 to 25 µg/dL (138 to 690 nmol/L) and doubles at 30 to 90 min, with a minimum of 20 µg/dL (552 nmol/L). Patients with Addison's disease have low or normal values that do not rise.
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How do you go about determining Cushing's Syndrome?
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To determine if there is glucocorticoid excess (Cortisol) - do a 24 urine cortisol to see if cortisol is elevated and ACTH is undetectable
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Where is renin produced? what does it affect?
what does it eventually help to release/ |
renin is produced by the juxaglomerular cells of the renal cortex.
Rate limiting step for Angiotensinogen to angiotensin I |
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What are aldosterone's effects?
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increase Na reabsorption in (NKCC, ENac, and NCC)
This can lead to hypokalemia and increase plasma volume through Na can also lead to hypertension |
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What can increased androgens in females lead to?
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facial and chest hair
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What can lead to male lactation?
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increase progesterone and prolactin then men can secrete milk especially if they have already developed breast buds
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Connection of the adrenal medulla with the autonomic nervous system?
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Medulla is just an extension of the autonomic nervous system
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Catecholamine biosynthesis pathway?
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tyrosine- DOPA- dopamine - NE - Epi
*NE and Epi have various receptors on different organs |
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Catecholamine biosynthesis pathway?
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tyrosine- DOPA- dopamine - NE - Epi
*NE and Epi have various receptors on different organs |
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What is a catecholamine's function?
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The major catecholamines are dopamine, norepinephrine, and epinephrine
*secreted from the medulla to respond to stress **part of the sympathetic nervous system |
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What is a pheochromocytoma?
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a tumor of the adrenal medulla with excessive amounts of the catecholamines
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What is the needed gene to turn on male sexual characteristics?
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SRY gene on the short arm of the Y chromosomes
*this switches on testicular development |
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What are the key genes in gonadal differentiation?
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*Gonad is bi-potential up to 40 days
*Dax1 and Wnt4 = ovary and a duplication of these genes also inhibit SRY *Wnt1 = testes pathway (only 1 copy needed) *Sertoli cell migration from mesonephros into the gonad * express 2 Sox-9 = further testicular development * leads to expression of SF-1 (gonad and adrenal gland (GnRH) formation) also necessary for expression of testosterone and AMH formation |
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What are the two cell types within male differentiation? What hormones do they secrete?
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-AMH (anti-mullerian) secreted at 7 weeks
- mullarian ducts are sensitive to this hormone at 9-12 weeks - Leydig secrete testosterone at 8-9 weeks - LH and hcG receptors are first present on the leydig cells at 10-12 weeks *suggesting the first secretions of testosterone are independent of LH and hCG |
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What happens if you have a defect in the AR enzyme?
the 5 alpha reductase enzyme? |
AR deficiency- won't stabilize male structures (internal or external) = look woman
5 alpha -internally a male but no external genitalia women to male |
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True or False:
Ovarian Development begins before testicular development? |
False; ovarian development starts later
*and begins whether or not the gram cells contain a normal XX (default) |
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What happens to the ovaries in Turner's syndrome?
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The ovary still develops germ cells BUT the ovaries degenerate in the 5th month of gestation because oocytes don't secrete the paracrine factors necessary to sustain their supporting cells = streak gonads
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Up until what week is the embryo sexually dimorphic?
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Week 7
* differentiation of the gonads begins at 7 weeks for the testes and 18 weeks for the ovaries |
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What steps are needed for this to differentiation to occur?
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Female: internal wolffian system degenerates and Mullerian duct system gives rise to the upper vagina, cervix, uterus, and fallopian tubes
Wolffian: AMH is secreted by the sertoli cells. Testosterone exerts its effects to bring about epididymis, vas deferens, and seminal vesicles. |
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External Genitalia differentiation?
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Mullarian: genital tubercle remains small and forms the clitoris. the urogenital slit remains open to form introitus (urethra and vaginal opening), labioscrotal folds - labia majora
Wollfian: the genital tubercle enlarges - penis, urogenital slit closes "posterior fusion", the labioscrotal folds develop into scrota |
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If a child is born sexually dimorphic or without some of the sex organs can male hormones be administered after birth to complete this process?
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No- these organs are only sensitive to these hormones in this fashion between weeks 7-14
once sexual differentiation occurs: *clitorsis growth arrest and penis keeps growing |
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What role does hCG play within male development?
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hCG is a stimulus for fetal testicular androgen secretion
*later with LH from the fetal pituitary the stimulation during the 16-20 week period gives a final burst of testosterone for the penis to reach its full gestational size |
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Summary of sexual dimorphism of embryos?
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Explain the mechanism for androgen action?
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1) testosterone diffuses into cells
2) 5 alpha reducatase converts some of the testosterone to DHT 3) DHT or T bind to AR 4) activates AR- binds to binding domain on DNA (acting as a transcription factor) |
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Why is DHT more potent than testosterone?
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DHT- AR has a more stable tertiary structure
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What is puberty?
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What is the minipuberty of the newborn? And by what mechanism do they believe it occurs?
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a time of increased pubertal hormone secretion
due to immaturity of the negative feedback system * lasts for about three months and there is little outward sign of these hormonal changes (erections and transient breast buds) |
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How is the quiescent phase (of hormones) achieved during childhood?
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Likely caused by highly sensitive hypothal-pit-gonadal negative feedback system
*LH and FSH are low during this time but still secreted in a pulsatile fashion * 6 months of age - 10 to 12 years of age |
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What is adrenarche?
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maturation of the adrenal gland
*occurs around 6 years of age * adrenal glands make the weak androgen DHEA-sulfate that increase slowly until late teens |
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What is gonadarche?
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maturation of the hypothalamic- pituitary gonadal axis
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Hypothalamic-pituitary gonadal axis
*What are the two distinct phases of puberty? |
Gonadarche and adrenarche
*Gonadarche involves maturation of the hypothalamic-pituitary gonadal axis = increase in GnRH secretion during SLEEP increasing LH response to GnRH *Adrenarche - maturation of the adrenal gland increased secretion of 17-KS in response to ACTH = growth of axil and pubic hair **Adrenarche is about 2 years before gonadarche |
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What is the purpose of contrasexual hormone type secretion?
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normal is up to 5% of the peak levels in the other sex
* testosterone brings about pubic hair in both sexes *Estrogen is responsible for breast development (some boys experience this transiently) * estrogen mediates some effects of testosterone on the neuroendocrine system and bone growth in males |
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What is this describing?
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min. puberty right after birth because mother's hormones are removed (decreased negative feedback)
*once adrenarche begins DHEA levels rise and first increase chemically - begins the rise in GnRH (FSH and LH) and gonadal and adrenal sensitivity * these increases are seen along with a decrease in negative feedback |
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what is this describing?
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FSH hormone higher in infancy
LH is higher after the onset of puberty *levels are low in childhood due to increased negative feedback *LH secretion patterns increase at NIGHT during puberty * are equal (day and night) through reproductive years * higher in menopause but equal du to the lack of negative feedback mechanisms |
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Pubertal Timing
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Girls ~ 10 3/4 years
Boys ~ 11 1/2 years |
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Puberty Milestones in North American Children
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What does Leptin regulate?
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Regulates food intake and energy expenditure at the hypothalamic level
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what is the link between puberty and nutrition?
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The link between Leptin and puberty?
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-Leptin is a hormone secreted from adipose tissue – it serves as a signal for the brain of the body’s energy stores
-There is strong positive correlation between leptin levels and percentage body fat -Thus, leptin is likely a “permissive” factor and not a trigger in the onset of human puberty. ** leptin level signal enough fat for puberty (no leptin receptors on GnRH) |
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What is a known signal for pubertal GnRH release?
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GPR54 and kisspeptin
*Kisspeptin influences the timing of puberty and the integration of nutritional and energy status - indirectly through leptin expression |
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How do Kiss-1 neurons integrate energy stores?
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-Kisspeptins act directly on GnRH neurons, which express GPR54, to stimulate the GnRH/gonadotropin axis
-Expression and function of the Kiss-1 system is sensitive to the state of energy reserves and metabolic factors -Adequate energy stores and metabolic state result in proper functioning of hypothalamic Kiss1, and thus the gonadotropic axis. -Leptin is likely to play an essential role in relaying information concerning the state of energy reserves and metabolism onto Kiss-1 neurons |
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Describe the 5 tanner stages in girls
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*this can be variable but typically between 2- 2.5 years between breast budding and menarche
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What occurs differently in the pubertal growth spurt between boys and girls?
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growth spurt is due to gonadal sex steroids, GH, IGF-1 increase
* boys and girls have difference in the timing of their peak (peak is later for boys- achieve taller heights) * the peak height is also greater for boys and more drawn out |
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What is considered percocious puberty?
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early onset of puberty
- anytime before age 8 in a girl or age 9 in a boy * to treat: GnRH agonist = constant level - decrease pulsitile actions |
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What is premature thelarche? how does it differ from precocious puberty?
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What is a better predictor or puberty: chronological age or bone age?
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most kids go into puberty when bone maturation hits a certain point
- nutrition need to obtain a certain body weight to undergo this |
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What is premature pubarche?
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isolated appearance of pubic hair prior to age 8 in girls and age 9 in boys
* normal growth and normal bone maturation |
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What is premature adrenarche?
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there is isolated pubic hair development AND biochemical evidence of the maturation of the adrenal gland (DHEA-sulfate level increases) = early maturation of zona reticularis
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If premature adrenarche occurs what are the associated risk factors?
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girls have a higher risk of polycystic ovarian syndrome
boys have a higher risk of developing insulin resistance later in life |
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What are the major causes of sexual precocity?
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What is the most significant consequence of untreated precocius puberty?
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rapid bone maturation
early epiphyseal fusion = short stature as an adult |
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What are the causes of delayed puberty?
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What defines delayed puberty?
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lack or incomplete development of the secondary sex characteristics by age 13 in girls and age 14 in boys
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Describe this slide?
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Pit-1 only expressed in the pituitary gland
*Pit-1 responsible for 3 specific cell types: GH, Prl, TSH *essential for formation and secretion of promotion Prop1 expression precedes Pit1 Hesx1 - restricted to Rathke's pouch- involved with the development of the optic nerve |
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What is involved in the patterning of the pituitary gland?
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1) outpouching of the ectodermal stomodeum (Rathke's pouch) - gives rise to the anterior lobe
2) evagination of the diencephalon gives rise to the posterior pituitary |
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What are the major factors affecting GH secretion?
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IGF-1 secretion by the liver is under the dual control of GH and nutrition
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How does GHRH stimulate GH?And how does SS inhibit GH?
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GHRH stimulates Gs protein coupled receptor on somatotrophs in the anterior pituitary - activating AC - accumulation of cAMP - activation of PKA- phosphorylation of CREB in nucleus = enhanced Pit-1 transcription - increased GH release
* SS inhibits by binding to the Gi receptor * |
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What type of pattern is GH released in?
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How does GH bind and signal to a cell?
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GH binds to 2 receptors causing dimerazation
dimerization leads to phosphorylation of JAK2 - cascade of phosphorylation including STATs - activation of gene expression |
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What is responsible for prenatal growth?
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IGF-1
*if you have a GH deficiency you are born with normal height and weight |
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What is the dual effect that GH stimulates growth?
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1) stimulates liver to secrete IGF-1 into the blood
2) induces the clonal expansion and differentiation of target stem cells(chondrocytes) then respond to GH by forming local IGF-1 as well as IGF01 receptors |
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What are some other effects of GH?
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-formation of IGF binding proteins
-raising blood sugar -lowering cholesterol |
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What are the two regulators of IGF-I?
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GH and nutrition
*GH is primary regulator when nutrition is normal *undernutrition - decreases IGF-1 but have normal or elevated GH * overnutrtion - IGF-1 levels are high while GH is decreased |
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What is the function of IGF-II?
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GH-independent IGF-II important role in fetal growth and repair of local tissue injury
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How many IGF-lignads? How many IGF receptors? And how many IGF BP?
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2 ligands/ 2 receptors / 6 binding proteins
* Both IGF I and II can bind to IGF-IR *IGF-II has growth promotion mainly through the IGF-IR *IGF-II can also bind to insulin receptor = mediates clearance of IGFII *80% of IGF-I is carried in the circulation by IGFBP-3 |
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Other Hormones affecting growth?
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Cortisol also important: necessary for GH secretion and cell multiplication
But if cortisol is in excess then in actually inhibits growth |
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What are the 4 phases of growth?
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Is size at birth more dependent on maternal environment or fetal genetic influences?
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Maternal environment
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Describe the chart for normal fetal growth
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gain length then weight
after birth have a higher weight velocity |
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Explain the interaction between fetus- mother- and placenta
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-mother supplies nutrients and oxygen via placenta and GH
-fetus in turn is in control of the placental production of hormones that regulate mother's metabolism (demand for nutrients) -placenta regulates fetal growth via production of GH and IGF and glucocorticoids(cortisol) |
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Prenatal vs. postnatal growth?
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prenatal growth is less dependent on factors important for postnatal growth : GH and Thyroid hormone
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IGF-I vs IGFII roles within growth?
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IGF-II has plasma concentrations 3-10X that IGF-I in late gestation
at birth- IGF-I levels rapidly increase due to the affects of GH on the liver IGFII- to IGFI shift is in response to the new environment |
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How does imprinting of genes affect growth?
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paternally expressed genes promote fetal growth
while maternally expressed genes limit growth so there is resources for future offspring |
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Postnatal growth is characterized by 3 components:
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infancy, childhood and puberty
infancy has the greater linear growth velocity, while childhood has a constant rate of (5-6cm/yr) and the great linear growth again during puberty |
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stasis in growth vs. saltation of growth
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stasis - nil over a 3 month period
saltation- bloom of growth *the timing of onset of adolescent growth spurt is the final determination of mature height. |
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Can have mutations in IGF-I and IGF-IR that leads to post natal growth failure and intrauterine growth retardation
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How does IGFIR copy number affect growth?
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What is Beckwith-Wiedemann syndrome?
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What is Russell-Silver Syndrome?
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What is short stature?
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How is a height projection done?
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Warning signs to potential growth problems?
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Classifications and causes of short stature?
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*intrinsic - inherent limitation of bone growth but parallel the normal percentiles
*delay = late bloomers * attenuated growth pattern - have subnormal growth rate- always has a pathological basis |
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untreated vs. treated growth hormone deficiency
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Is GH indicated for Turner's syndrome?
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What are the classifications of tall stature?
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What do the growth curves for intrinsic, advanced and precocious puberty look like?
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-intrinsic - familial or marfan = longed bone (normal birth weight)
- advanced - child is tall but ends up normal size adult - go into puberty earlier therefore bone age advances sooner and end up a normal adult precocious puberty - premature exposure of bones to sex hormones advances bone maturation - growth ceases at an early age and end up short |
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What happens with hyper-secretion of GH?
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rare disorder but the pituitary gigantism results; caused by a tumor and secrete excess GH but decreases secretion of GRH and sex hormones
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What are the two embryonic origins of the thyroid gland?
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central anlagen from the arterial pharyngeal floor and the two lateral anlagens develop from the 4th and 5th pharyngeal pouch.
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What controls the normal migration of the thyroid gland?
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TTF-1
*thyroglossal cyst *sublingual *lingual * intralingual |
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How are the thyroid hormones made?
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-T4 inactive but most abundant
-T3 is active -These both are hooked to various binding proteins to go to the needed tissues -Once there the T4 can be activated to T3 – then this is another level of regulation so that the tissues can decided how much they actually need |
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Name the major proteins of thyroid hormone synthesis
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-Na/I Symporter
* transports iodine into the cell *basal side *also transports: ClO3-, SCN-, Br- - Thyroglobin (TG) * martrix for iodination and hormonogenesis *follicular lumen *TFF1 & Pzx* *increase in response to TSH - Thyroperoxidase (TPO) *catalyze oxidation reaction of I- and coupling *Heme containing enzyme * Apical membrane |
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What is one main function of the thyroid?
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thyroid concentrates inorganic iodide from the extracellular fluid by active energy dependent process
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What is organification?
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biochemical process that takes place in thyroid glands. It is the oxidation of iodide by peroxide, and then its binding to tyrosyl residues within the thyroglobulin molecule
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Under normal conditions which is greater: the rate of inward clearance of iodidie by the thyroid or the rate of incorporation of iodide into aa?
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The rate of inward clearance of iodide by the thyroid exceeds the rate of incorporation of iodide into aa (organification)
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True or False: TSH doesn't not stimulate iodide transport?
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False
TSH does stimulate Iodide transport *increasing glandular content of organic iodide transport diminishes iodide transport in response to TSH (negative feedback mechanism) |
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Name the major proteins of thyroid hormone synthesis
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-Na/I Symporter
* transports iodine into the cell *basal side *also transports: ClO3-, SCN-, Br- - Thyroglobin (TG) * martrix for iodination and hormonogenesis *follicular lumen *TFF1 & Pzx* *increase in response to TSH - Thyroperoxidase (TPO) *catalyze oxidation reaction of I- and coupling *Heme containing enzyme * Apical membrane |
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What is one main function of the thyroid?
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thyroid concentrates inorganic iodide from the extracellular fluid by active energy dependent process
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What is organification?
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biochemical process that takes place in thyroid glands. It is the oxidation of iodide by peroxide, and then its binding to tyrosyl residues within the thyroglobulin molecule
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Under normal conditions which is greater: the rate of inward clearance of iodidie by the thyroid or the rate of incorporation of iodide into aa?
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The rate of inward clearance of iodide by the thyroid exceeds the rate of incorporation of iodide into aa (organification)
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True or False: TSH doesn't not stimulate iodide transport?
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False
TSH does stimulate Iodide transport *increasing glandular content of organic iodide transport diminishes iodide transport in response to TSH (negative feedback mechanism) |
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How does perchorate and thiocyanate affect iodide transport?
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Both of these molecules block or increase iodide efflux
*inhibiting iodide transport |
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What is the Wolff-Chaikoff effect?
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reduction in thyroid hormone levels caused by ingestion of a large amount of iodine
?? It is an autoregulatory phenomenon that inhibits organification (oxidation of iodide) in the thyroid gland, the formation of thyroid hormones inside the thyroid follicle, and the release of thyroid hormones into the bloodstream. |
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What composes MIT? DIT?
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tyrosine residues on the thyroglobulin molecule are iodinated to produce monoidotyrosine (MIT).
Subsequent iodination of MIT - produces diiodotyrosine (DIT) |
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How is T4 synthesized?
How does that differ from T3 synthesis? |
T4 is made when two molecules of DIT are coupled on to the thyroglobulin backbone = thyroxine
T3 is synthesized when DIT and MIT couple together *stored in the colloid cell of the thyroid follicle |
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The metabolism of T3 and T4 into active and inactive intermediates involves the action of 3 types of deiodinases. The thyroid gland secretes approximately 100 μg of T4 and 6 μg of T3 daily.[87] An additional 24 μg of T3 is produced as a result of the deiodination of T4 in extrathyroidal tissues.[87] Thyroid hormone is activated when the prohormone T4 is converted to the active hormone (T3) through the removal of an iodine atom from its outer ring and deactivated when an iodine atom is removed from its inner ring (which converts thyroxine to the inactive rT3). Deiodination occurs mainly within the cells; thus, cell-specific deiodinases play an important role in determining the activity of thyroid hormone. Three deiodinases are found in humans: (1) Type 1 (found mainly in the liver and kidney), which can remove iodine both rings; (2) Type 2 (found mainly in skeletal muscle and in the heart, fat, thyroid, and central nervous system [including the brain]), which can induce deiodination in the outer ring, making it the main activating enzyme; and (3) Type 3 (found in fetal tissue and in the placenta), which induces deiodination in the inner ring only and, thus is the main inactivating enzyme. Approximately 20% of T3 is actually made in the thyroid gland. It has been observed that tissues in need of thyroid hormone convert T4 to T3 at different rates; therefore, the administration of T3 as well as T4 may be a better solution for hypothyroidism than T4 alone.[88]
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What organ systems does the thyroid affect?
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What is this showing?
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*thyroid hormones enter the cell through a concentration dependent passive diffusion
* T3 is biologically active form and either diffuses in or is converted from T4 * T3 moves into the nucleus where it interacts with thyroid hormone receptors (TRs) |
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*possess two TR genes alpha and beta (chromosome 17)
* TR bind to cognate response elements (TREs) on target genes ** when Thyroid hormone is absent the TR recruit a co-repressor |
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*TR has a well conserved DNA binding domain separated from the carboxyl terminal ligand binding domain
*Hinge domain has recently been shown to interact with corepressor * the amino terminal does not appear to play a role in the TR- mediated repression or transactivation |
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*TR has a well conserved DNA binding domain separated from the carboxyl terminal ligand binding domain
*Hinge domain has recently been shown to interact with corepressor * the amino terminal does not appear to play a role in the TR- mediated repression or transactivation |
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co-repessors are bound to TR in absence of thyroid hormone
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when the thyroid hormone is present it binds to TR and then a coactivator binds to TR to start transcription
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What are the effects of thyroid on cardiac function?
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Define hypo and hyper thyroid?
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Everything else is working so the TSH levels are high and the TRH levels as well because it is only the thyroid part that isn’t working
If the thyroid is high then this makes the serum concentrations of TSH and TRH low (due to negative feedback mechanisms) |
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What are the functions that are increased by T3?
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- oxygen consumption
-heat production - metabolic rate -lipid synthesis - lipid oxidation - cholesterol synthesis and degradation - protein synthesis and degradation - drug metabolism |
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Difference in concentration between hormones and stimulates of hypo and hyper-thyrodism?
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What effect does increase T3 have on the vascular system?
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Vasodilation
decrease: Hypertension |
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What effect does increase T3 have on the skin?
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warm, smooth, and moist
decrease: rough and dry |
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What effect does increase T3 have on the gastrointestinal?
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increased motility and absorption
Decrease: decrease in motility |
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What effect does increase T3 have on the skeletal?
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increased bone turnover
decrease: decrease in bone turnover |
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What effect does increase T3 have on the neuromuscular?
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hyperactivity- increased muscle contraction
decrease: lethargy and slow muscle relaxation |
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What defines hypothyroidism?
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Heart function isn’t that great so you become cold and lethargic/ fatigue
Tired all the time Impaired concentration Weight gain and constipation – decreased motility within the gut |
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What defines hyperthyroidism?
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Fatigued
Heat intolerance – constantly hot – vasodilatory effects Resting tremors-increased muscle contraction Diarrhea and lose weight – increased gut motility The goiter can be one the sides as well |
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What happens to diabetes risk with increasing BMI
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diabetes type II increases with increasing BMI
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What does energy balance have to do with obesity?
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How does the hypothalamus function as the central regulator of energy?
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Name some anorexigenic and orexigenic neuropeptides & neurtransmitters
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What is the function of the central arcuate nucleus?
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* processes these different inputs and exerts its effects by signaling to various effector neurons
*Arcuate nucleus – paraventricular nucleus – lateral hypothalamic nucleus *Insulin –signal of the level of adiposity over a moderate to long term period – stimulates POMC and CART = anorexigenic effects & inhibtis AGRP/NPY neurons *Lepin – principle adiopcyte number and fat content – long term regulation – promotes anorexigenic effects |
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Is ghrelin a orexigenic or anorexigenic peptide?
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Orexigenic peptide
*secreted by the stomach and duodenum - serum levels rise before eating and decrease after eating |
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What is the function of YY3-36 (secreted by distal GI tract on the ingestion of food)?
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Binds to the Y2 receptor that is located in the NPY (orexigenic nucleus) and inhibit the orexigenic effects - decreasing food intake
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What happens with increasing adiposity?
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leptin consequently rises and has a limited effect on reducing good intake and adverting obesity
*might be due to leptin resistance or decreased leptin transport |
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What does POMC undergo that is different from other neurotransmitters/neuropeptides?
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Mutations in this gene have been associated with early onset obesity(MSH decreases food intake), adrenal insufficiency(ACTH), and red hair pigmentation
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What is the mechanism behind Neuropeptide Y
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* role in inducing hunger
*Injecting this hormone can increase body fat because it turns off or down the sensor that tells you that you are full |
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What relays signals from the GI tract (ghrelin, CCK, PYY, insulin) to the hypothalamus?
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Nucleus Tractus Solaris
*Senses the presence or absence of food in the gut and signals to the brain to regulate short term appetite and satiety (lack of hunger) |
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What are the effects of ghrelin?
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When are ghrelin levels the highest? what does ghrelin potentially regulate? stimulation of food intake by ghrelin depends on what?
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*Ghrelin levels are highest in the fasting state
* might be involved in meal initiation and day to day food intake * depends on an intake vagal nerve **Ghrelin is suppressed in obesity |
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What are the two stimulators for adipogenesis?
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1) PPAR-gamma - differentiation
2) cortisol - stimulates lipoprotein lipase |
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Adipocyte hypertrophy vs. Adipocyte hyperplasia
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hypertrophy - increase in size
hyperplasia - increase in number |
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Visceral vs. Subcutaneous fat?
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Visceral - fat laid down on organs = orange shape
Subcutaneous- fat laid down subcutaneously = pear shape |
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What is the function of leptin?
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Leptin signals to the brain that the body doesn't need anymore food.
*lower leptin production increases food intake |
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What are the characteristics of Leptin?
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Along with Leptin what else inhibits food intake?
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CCK
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What is Peptide YY's action on food intake?
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-member of the NPY family (orexigenic)
- binds to the Y2 receptor and inhibits orexigenic effects and stimulates MSH effects (anorexigenic) |
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What is the difference between lepfin and PYY?
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obese patients don't exhibit a PYY resistance where they usually exhibit a leptin resistance
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What is the relationship between BMI and PYY?
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As BMI increases then PYY decreases
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What is PP? And what effect does it have on food intake?
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PP is a hormone produced by the PP cells of the Islets of Langerhans
*reported to reduce appetite * effects are sustained from evening until next morning * its receptor Y4R is found in brainstem and arcuate nucleus |
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What effect does GLP-1 have on food intake?
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GLP-1 is released from the gut in response to nutrient intake
*stimulates insulin release ( because due to food intake glucose levels will soon be high) * found in brainstem, acruate nucleus, and PVN * decreases food intake - by decreasing gastric emptying |
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What effect does Oxyntomodulin have on food intake?
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oxyntomodulin is released from the intestines postprandially and inhibits food intake
* does so with greater potency that GLP-1 (different pattern of neuronal activation) * fasting levels of ghrelin were significantly suppressed by Oxm |
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What are the functions the female reproductive system?
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What regulates gonadotropin release?
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What is the function of FSH?
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promotes follicle development
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What is the function of LH?
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promotes corpus luteum
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Oocyte development within follicles?
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Estrogen is responsible for?
Progesterone is responsible for? |
Estrogen is responsible for proliferation, while progesterone is responsible for differentiation
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What occurs during the corpus luteal phase?
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What surrounds the egg during ovulation?
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cumulus oophorus
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Compare the ovarian and uterine phases of the menstrual cycle?
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Follicular (ovary) ~ Proliferative (uterus)
Luteal (ovary) ~ Secretory (uterus) |
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What are the time differences in cycles due to?
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The difference in the follicular phase (the luteal phase is religiously 14 days after ovulation)
*follicular phase decreases with increased reproductive age |
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What can you measure to determine if ovulation has occurred or not?
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The high progesterone levels
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What is the required enzyme to make estrogens from androgens?
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Describe ovarian steroid hormone synthesis?
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Theca cells express LH receptors then LH binds and stimulates androgen production
Androgens move into GC area which express aromotase to make estrogens *increased local estrogen levels |
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Describe 2 cell, 2 gonadotropin theory
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TC have LH receptors - produce androgens
Androgens diffuse into GC area GC have FSH receptors - produce estrogens *FSH receptors increase aromatase ** GC get LH receptors later and this is what triggers ovulation in the mature follicle |
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How does GnRH regulate the release of two different hormones?
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GnRH pulsitility of GnRH is very important - determines what is secreted
* High frequency favors LH * Low frequency favors FSH **Abnormal GnRH pulse disrupts menstrual cycels * GnRH agaonist - desensitizes reproductive system - decreases LH and FSH |
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What occurs during desensitization?
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Gonadotropin release during menstrual cycle
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What is this showing?
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pulsitility of GnRH
*rising progesterone and estrogen levels from the uterus feedback and shot off LH and FSH secretion |
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How does estrogen and progesterone affect LH and FSH secretions?
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When does estrogen and progesterone have a positive feedback affect?
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steady increase in estrogen and a little progesterone influences the pulsitility of GnRH which ultimately causes the LH surge = ovulation
* this all needs to happen correctly so that they hormones don't cause a negative feedback on GnRH and the pituitary |
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What induces the LH surge?
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tiny bit of progesterone from GC (from ovary) promotes LH surge with estrogen
*initially FSH is higher - this develops the follicle then aromatase is active and estrogen can be made *LH continues to decrease when there is no pregnancy |
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Inhibin is an ovarian peptide hormone. What is its function?
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*inhibin B is the marker for GC function
- it is secreted by pre-antral and antral follicles - stimulated by FSH - increased during follicular phase Inhibin A: marker of corpus luteum function - antral follicles and corpora luttea -stimulated by LH - increased during luteal phase **made in granuolsa cells and goes back to pituitary to shut of FSH |
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Activin is an ovarian peptide hormone. What is its function?
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What is the function of follistatin?
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When do Inhibin A vs B levels rise during the cycle?
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How is the dominant follicle selected?
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pre-antral to antral the estrogens rise so much so that they have a negative feedback effect on the FSH (decreases)
- then the follicle with the most FSH receptors that can make more estrogens wins. |
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What occurs during ovulation?
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LH surge allows prostaglandins to be secreted to separate out connective tissue in the follicle
Progesterone is also secreted - acts as a smooth muscle relaxant and enhance proteolytic enzyme digestion - also places more LH receptors on the cell |
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Does every cell have every enzyme?
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No GC cells do not have 17 alpha - this is why LH receptors on TC have to deliver androgens so progesterone can be made
During Luteal phase the cells have SCC to make progesterone but lack 17 alpha- this way progesterone gets built up for the luteal phase |
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How doe Birth Control Pills work?
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Hormone withdrawal bleed not a true menstrul period
* estrogen and progesterone are taken every day - body cells cease to make estrogen - sugar pills FSH and LH begin to rise again after 7 days then you start new pack |
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How do fertility drugs work?
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How does the ovary develop?
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In fertility treatment why is hCG given over LH?
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What role does hCG play in maintaining an early pregnancy?
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supports corpus luteum to low continuing increase in progesterone until placenta takes over at 10 weeks
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What is the function of progesterone throughout the pregnancy?
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How does the placenta make estrogens if there is a progesterone block?
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The mother has to obtain androgens(DHEA) from the baby then move to placenta where aromatase is present and can make estriol
*another way to know that fetus is alive is estriol is in the mother's pee) *the fetus conjugates steroid to sulfate as a protective agent so the placenta has to use sulfatase to deconjugate the steroid to make estrogen |
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What is the role of oxytocin during labor?
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What occurs during parturition?
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CRH might be the clock that starts the process
* preterm babies have high CRH and post term babies have low CRH * pituitary volume doubles in size during pregnancy |
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How does the mammary gland develop?
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What two hormones does nursing have an effect on?
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What is prolactin's hypothalamic releasing factor?
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if you increase Prl you increase Dopomine = prolactin inhibiting its own release
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What is lactational amenorrhea?
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What are the responses to Insulin?
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Compare glucose uptake for lean, obese, and NIDDM
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Lean- with exercise you are more sensitive to insulin
Obese- ability to increase glucose uptake with infused with insulin - insulin resistance = insulin is less effective NIDDM- response to insulin is markedly reduced |
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Compare glucose uptake for a lean, obese, and NIDDM individual?
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Lean- increase insulin sensitivity with exercise
Obese- ability to increase glucose uptake when infused with insulin - but insulin resistance = insulin less effective NIDDM- response to insulin is markedly reduced |
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Describe glucose metabolism?
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- all important enzymes are regulated by insulin
- pancreatic Beta cells sense glucose to know how much insulin should be secreted |
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insulin binds to receptor
insulin receptors on most tissues: the most important ones being liver and muscle * insulin binding domain (alpha) actives the TK domain (beta) then these phosphorylate substrates |
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What are the two directions the insulin signaling network can work through?
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MIP- kinase = cell growth and differentiation
PI3 = metabolic actions - glucose metabolism and lipid synthesis * in an insulin resistant person there are profound defects in the insulin signaling pathway |
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What are the functions of the testes and what are the functions of the accessory ducts?
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What is the pathway of the sperm?
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What are the embryonic origins of the bi-potential gonad?
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sertoli and GC - coelomic
sperm and oocyte- germ cell Leydig and TC- mesenchymal |
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What is the organization of the seminiferous tubule?
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What is the two cell, two gondatropin theory for testes?
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What is the enzyme that mediates cholesterol to prognenolone?
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What are the three places that aromatase is located?
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1) GC
2) Brain - masculinization in males 3) Adipocytes |
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What are the differential effects between testosterone and DHT?
|
DHT is more potent and doesn't really circulate ( just located in its site of action - hair follicles and external genitalia)
* also responsible for male patterned baldness |
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What happens during 5 alpha reductase deficiency?
|
there are two forms of 5a reductase the fetal and adult form
*when there is a fetal deficiency the babies are born with ambiguous genitalia then when puberty arrives the adult 5a kicks in and external genitalia develop |
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How is most testosterone found throughout the body?
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1) bound hormone can not bind to receptor
2) bound to sex hormone binding globulin and albumin 3) sertoli cells synthesize androgen binding protein - secreted into the lumen of the seminiferous tubules |
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Sperm development
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On average how long does spermatogenesis take?
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70 days
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What do sertoli cells and leydig cells provide for spermatogenesis?
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What happens if seminal fluid reaches past the vagina?
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Causes horrible cramps in the women because it contains many prostaglandins
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What is Capitation?
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What occurs when the sperm encounters to oocyte?
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The cumulus surrounding the oocyte is important for the sperm finding the egg
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How do the sperm bind to the Zona Pellucida?
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Describe the acrosome reaction?
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Describe the acrosome reaction?
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Describe the penetration of the Zona Pellucida?
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How does the sperm bind to the egg?
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Describe egg activation?
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What is the difference between using a GnRH agonist and a GnRH antagonist?
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How do Birth Control Pill help Acne and Hirsutism?
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