The major role of the HPA axis is to mediate the neuroendocrine stress response, in order to reestablish body homeostasis after an acute stressor (4).A principal component of the stress response is the CRH system, which is located in the paraventricular nucleus (PVN) of the hypothalamus. CRH is synthesized by neurons in the parvocellular/small cell division of the PVN, and it is secreted into the pituitary portal blood (5-7). CRH via portal blood enters the anterior pituitary and binds to type 1 CRH cell-surface receptors, resulting in ACTH secretion (8-10). ACTH acts on the adrenal cortex, specifically on the zona fasciculata, to stimulate cortisol secretion (11). Cortisol inhibits the secretion of CRH and ACTH from the hypothalamus and anterior pituitary, respectively (11).
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However, acute physical or psychological stress will activate the HPA axis, resulting in increased plasma ACTH and cortisol levels (11). The stressor activates the HPA axis by stimulating the hypothalamus to release CRH (13). Once cortisol is released from the adrenal cortex in response to ACTH stimulation, it functions to increase blood glucose levels through its action on glycogen, protein, and lipid metabolism. In the liver, cortisol stimulates gluconeogenesis and, in adipose tissue, activates lipolysis and free fatty acids (FFA) to be released into the circulation. Cortisol also has a permissive effect on glucagon and catecholamine action, thereby contributing to insulin resistance and increased blood glucose levels at the expense of glycogen, protein, and lipid storage (11). Among the two receptors identified for CRH, CRHR1 has higher affinity for rat/human CRH than CRHR2, even though the two receptors share 70% sequence identity (14,
However, acute physical or psychological stress will activate the HPA axis, resulting in increased plasma ACTH and cortisol levels (11). The stressor activates the HPA axis by stimulating the hypothalamus to release CRH (13). Once cortisol is released from the adrenal cortex in response to ACTH stimulation, it functions to increase blood glucose levels through its action on glycogen, protein, and lipid metabolism. In the liver, cortisol stimulates gluconeogenesis and, in adipose tissue, activates lipolysis and free fatty acids (FFA) to be released into the circulation. Cortisol also has a permissive effect on glucagon and catecholamine action, thereby contributing to insulin resistance and increased blood glucose levels at the expense of glycogen, protein, and lipid storage (11). Among the two receptors identified for CRH, CRHR1 has higher affinity for rat/human CRH than CRHR2, even though the two receptors share 70% sequence identity (14,