Regulation of Cortisol Secretion

The principal regulator of cortisol secretion is ACTH (see Chapter 31), the release of which is regulated by CRH and by circulating unbound cortisol. The balance of the effects of CRH and cortisol on the anterior pituitary maintains fairly constant ACTH stimulation of the adrenals and circulating levels of cortisol. This closed-loop feedback system is superseded by neural signals from higher regions of the brain in nonsteady-state conditions (e.g., circadian rhythm, stress). 

ACTH exerts effects on the zona fasciculata by surface binding, calcium-dependent activation of membrane-bound adenylate cyclase and intracellular cAMP mediation. It increases activities of cholesterol esterase and cholesterol side-chain cleavage enzyme (CYPI 1 A), thereby stimulating production of pregnenolone. Cholesterol side-chain cleavage enzyme is a cytochrome P-450 enzyme present in mitochondria. ACTH promotes the 

Regulation of renin release. Numbers 1-7 indicate the steps involved in the secretion of renin by the juxtaglomerular apparatus and its action. , Stimulatory, inhibitory f increa.sed production. 

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FIGURE 74-3. Negative feedback system involved in the regulation of cortisol secretion under normal conditions. CRH, corticotropin-releasing hormone ACTH, adrenocorticotropic hormone. 

F. 43.7. Regulation of cortisol secretion. Various factors act on the hypothalamus to stimulate the release of corticotrophin-releasing hormone (CRH). CRH stimulates the release of ACTH from the anterior pituitary, which stimulates the release of cortisol from the adrenal cortex. Cortisol inhibits the release of CRH and ACTH. 

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