Figure 1 presents the individual steroid structures that sequentially form the metabolic pathways of the adrenal cortex steroids that describe the biosynthesis of the glucocorticoids, mineralocorticoids, and the androgen dehydroepiandrosterone (DHEA). As discussed in Chapter 10 and illustrated in Figure 1, the adrenal cortex is anatomically divided into three zones that produce the three different major classes of the adrenal steroids; these are the green panel zona glomerulosa (mineralocorticoids), the peach panel zona fasciculata (glucocorticoids), and the blue panel zona reticularis (androgens). Over 45 steroids have been isolated and chemically characterized from human adrenal gland extracts.
Fig1. Adrenal cortex pathways for production of three classes of steroid hormones. Cholesterol and the presence of the cholesterol side chain cleavage enzyme are the starting point of separate steroid hormone(s) biosynthesis for the three classes. The zona glomerulosa (mineralocorticoids) produces aldosterone. A structural hallmark of aldosterone is the presence of both a C-11 hydroxyl and a C-18 aldehyde. The C-18 aldehyde can form either a five member hemiacetal ring, which uses the C-11 hydroxyl group or a six member hemiacetal ring, which uses the C-21 hydroxyl group. These are reminiscent of carbohydrate chemistry. The zona fasciculata (glucocorticoids) produces both cortisol and corticosterone. The zona reticularis produces limited amounts (represented by the dashed arrow) of the androgens, dehydroepiandrosterone (DHEA), androst-4-ene-3,17-dione and testosterone. DHEA can be converted to DHEA-sulfate via a sulfotransferase, which forms a mixed ester with the 3β-hydroxyl group. For each of the steroid enzyme transformations, the 3-7 letter/number acronymn is shown in magenta next to the arrow.
The 21-carbon corticosteroids include the glucocorticoids and the mineralocorticoids; both subclasses are produced by the adrenal cortex (see Chapter 10). The corticosteroids are characterized by (i) an oxo group at carbon-3 linked wth a Δ4,5 double bond; (ii) a two-carbon side chain on carbon-17; (iii) an oxo group at carbon-20; and (iv) a hydroxyl on carbon-21. Glucocorticoids are characterized by the presence or absence of hydroxyls at both carbon-11 and carbon-17. The principal glucocorticoid in humans is cortisol.
The principal mineralocorticoid in humans is aldosterone. Mineralocorticoids are characterized by a hydroxyl at carbon-11 and an aldehyde on car bon-18 (that is produced by oxidation of a carbon-18 hydroxyl). As a consequence of its carbon-18 aldehyde moiety, aldosterone can form a five-membered hemiacetal ring by linking the C-18 aldehyde with the car bon-11 hydroxyl or, alternatively, linking the C-18 aldehyde with the carbon-21 hydroxyl to create a six membered hemiacetal ring.
As indicated in Figure 1, the zona reticularis of the adrenal cortex has the enzymatic capability to produce steroids with mild androgenic activity. The principal adrenal androgens are dehydroepiandrosterone (DHEA) and 4-androstene-3,17-dione. The production of these and related steroids may increase in some instances adrenal tumors; women with such tumors may develop secondary male characteristics, including beard growth and hirsutism.
