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. 2023 Apr 12;19:811–828. doi: 10.2147/NDT.S402831

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© 2023 Kanes et al.

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AVP and CRH stimulate ACTH secretion by pituitary corticotrophs. (A) In the basal state, the HPA axis releases glucocorticoids according to ultradian and circadian rhythms. (B) Activation by an acute physical or emotional stressor triggers synthesis and release of CRH and AVP from the hypothalamus to the pituitary, where they bind to the CRH1 and V_1b receptors, respectively, to trigger ACTH release. ACTH acts on the adrenal cortex to stimulate production and release of glucocorticoids, which serve as key allostatic mediators of brain function and behavior and regulate upstream steps via positive and negative feedback loops. (C) During chronic (repeated) stress, AVP is upregulated, CRH is downregulated, and AVP-mediated stimulation of ACTH release is refractory to negative glucocorticosteroid feedback due to enhanced responsivity of PKC-mediated stimulation of ACTH release by glucocorticosteroids.

Note: Data from these studies.⁹^,¹¹⁹^,¹²⁰^,¹⁵¹^,¹⁹⁹^,²⁰⁰

Abbreviations: ACTH, adrenocorticotropic hormone; AVP, arginine vasopressin; cAMP, cyclic adenosine monophosphate; CRH, corticotropin-releasing hormone; CRH1, CRH 1; HPA, hypothalamic-pituitary-adrenal; IP₃, inositol 1,4,5-trisphosphate; PKA, protein kinase A; PKC, protein kinase C; PLC, phospholipase C; V_1b, vasopressin 1b.