The adrenal cortex releases a large number of steroids into the circulation. Some have minimal biologic activity and function primarily as precursors, and there are some for which no function has been established. The hormonal steroids may be classified as those having important effects on intermediary metabolism and immune function (glucocorticoids), those having principally salt-retaining activity (mineralocorticoids), and those having androgenic or estrogenic activity (see Chapter 40). In humans, the major glucocorticoid is cortisol and the most important mineralocorticoid is aldosterone. Quantitatively, dehydroepiandrosterone (DHEA) in its sulfated form (DHEAS) is the major adrenal androgen. However, DHEA and two other adrenal androgens, androstenedione and androstenediol, are weak androgens and androstenediol is a potent estrogen. Androstenedione can be converted to testosterone and estradiol in extra-adrenal tissues (Figure 39–1). Adrenal androgens constitute the major endogenous precursors of estrogen in women after menopause and in younger patients in whom ovarian function is deficient or absent.
17˛-Hydroxylase 17, 20-Lyase CH3 (P450c17) CH3
COO2AcetateCholesterol(ACTH?)NADPHHOCH3COOCH2OHCOOCH2OHCOOHOCorticosteroneCH2OHCOHOCHOAldosterone11-Deoxy-corticosteroneProgesteronePregnenoloneCOOHHO17-Hydroxy-pregnenoloneOHODehydroepi-androsteroneOO˜4-Androstene-3,17-dioneTestosteroneEstradiolAndrogen and estrogen pathway Glucocorticoid pathway Mineralocorticoid pathway CH3COOHO17-Hydroxy-progesteroneCOOHO11°-Deoxycortisol3°-Dehydrogenase ˜5,˜4-Isomerase NAD+ 11°-Hydroxylase (P450c11) 21˛-Hydroxylase (P450c21) CH2OHCOOHOHOCortisolCH2OH
FIGURE 39–1 Outline of major pathways in adrenocortical hormone biosynthesis. The major secretory products are underlined. Pregnenolone is the major precursor of corticosterone and aldosterone, and 17-hydroxypregnenolone is the major precursor of cortisol. The enzymes and cofactors for the reactions progressing down each column are shown on the left and across columns at the top of the figure. When a particular enzyme is deficient, hormone production is blocked at the points indicated by the shaded bars. (Reproduced, with permission, from Ganong WF: Review of Medical Physiology, 22nd ed. McGraw-Hill, 2005. Copyright © The McGraw-Hill Companies, Inc.)
Cortisol (also called hydrocortisone, compound F) exerts a wide range of physiologic effects, including regulation of intermediary metabolism, cardiovascular function, growth, and immunity. Its synthesis and secretion are tightly regulated by the central nervous system, which is very sensitive to negative feedback by the circulating cortisol and exogenous (synthetic) glucocorticoids. Cortisol is synthesized from cholesterol (as shown in Figure 39–1). The mechanisms controlling its secretion are discussed in Chapter 37.