estradiol estrone estradiol

FIGURE 6 Biosynthetic pathway for androgens and estrogens. In the adrenal the sequence does not usually proceed all the way to testosterone and the estrogens, which are the gonadal hormones. Because the cells of the zona glomerulosa lack 17a-hydroxylase, these reactions can occur only in the inner zones.

products of the same enzyme that catalyzes 17a-hydroxylation in the adrenals and the gonads, cleavage of the bond linking carbons 17 and 20 in the adrenals normally occurs to a significant extent only after puberty, and then is confined largely to cells of the zona reticularis.

Steroids of the 18-carbon series usually have estrogenic activity. Estrogens characteristically have an unsa-turated A ring. Oxidation of the A ring (a process called aromatization) results in loss of the methyl carbon at position 19 (Fig. 6). This reaction, which takes place principally in ovaries and placenta, can also occur in a variety of nonendocrine tissues where aromatization of the A ring of either testicular or adrenal androgens comprises the principal source of estrogens in men and postmenopausal women.

Regulation of Adrenal Cortical Hormone Synthesis

Effects of ACTH

Adrenocorticotropic hormone maintains normal secretory activity of the inner zones of the adrenal cortex. After removal of the pituitary gland, little or no steroidogenesis occurs in the zona fasciculata or reticu-laris, but the zona glomerulosa continues to function. In cells of all three zones, ACTH interacts with a specific G-protein-coupled membrane receptor and triggers production of cyclic AMP by activating adenylyl cyclase (see Chapter 2). Cyclic AMP activates protein kinase A, which catalyzes the phosphorylation of a variety of proteins and thereby modifies their activity. In the zonae fasciculata and reticularis this results in accelerated de-esterification of cholesterol esters, increased transport of cholesterol to the mitochondria, and increased synthesis



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