Corticotrophin releasing hormone (CRH) is secreted from the hypothalamus in a diurnal pattern. Adrenocor-ticotrophic hormone (ACTH) is secreted by the pituitary in response to CRH that in turn activates the enzyme desmolase in the adrenal glands converting cholesterol to pregnenolone. This is the ratelimiting step for the production of all the adrenocortical hormones. Cortisol is mainly controlled in this way, aldosterone is mainly controlled by the reninangiotensin system, and androgens
Aldosterone is the corticosteroid with the most mineralocorticoid activity, socalled because it controls sodium, potassium and water balance. Its production is stimulated mainly by the reninâ€“angiotensin system. Renin is secreted from the juxtaglomerular apparatus in the kidney in response to reduced renal blood flow, for example due to hypotension. In response aldosterone acts on the kidney and vasculature (see Fig. 11.9).
When aldosterone levels are high this may be due to high renin levels (secondary hyperaldosteronism) or it may be independent of renin production (primary hy-peraldosteronism).
Cortisol is the major glucocorticoid, although aldosterone and corticosterone also have some effect. The glucocorticoids control glucose metabolism, for example gluconeogenesis, and mobilisation of fat stores (lipolysis) amongst other actions. Cortisol exerts a negative feedback on ACTH and CRH secretion. Glucocorticoids are most important during fasting, illness or surgery (see Fig. 11.10).
Androstenedione is produced by the adrenal cortex and is converted to testosterone and dihydrotesterone. In males, 95% of active testosterone is derived from the testis, so adrenal androgen excess or deficiency is relatively insignificant. In females 50% of the peripheral production of testosterone is from adrenal androgens. Female neonates with congenital adrenal hyperplasia have ambiguous genitalia (clitoromegaly). Adults with Cushingâ€™s syndrome and adrenal tumours with hyper-secretion of adrenal androgens have acne, hirsutism and virilisation.