Conversion of 17-hydroxypregnenolone to cortisol by normal and hyperplastic human adrenal slices

Progesterone 1 is a metabolic precursor common to cortisol and corticosterone biosynthesis in the adrenal cortex. However, incubation of radioac-tive progesterone with bovine adrenal homogenates (1) and human adrenal slices (2, 3) yields corti-costerone with a specific activity greater than that of cortisol, even though the amount of cortisol produced is greater. Although hypotheses involv-ing enzyme kinetics have been suggested to explain these results, other pathways of cortisol biosynthe-sis may exist that do not involve progesterone. The pathway from progesterone to cortisol is believed to be via 17-hydroxyprogesterone- * 11-deoxycortisol-> cortisol (4). Progesterone is de-rived from A5-pregnenolone upon oxidation of the 3,8-hydroxyl group and a shift of the double bond. Hydroxylation of A5-pregnenolone to 17a-hydroxy-A5-pregnenolone is considered the first step in adrenal androgen biosynthesis (5). Conversion of 17-hydroxy-A'5-pregnonolone to 17a-hydroxy-pro-gesterone by oxidation of the 3/3-hydroxyl group and a shift of the double bond appeared to be a reasonable alternative possibility for cortisol bio-synthesis. Indeed, Weliky and Engel (6) re-ported that 17-hydroxy-_A5-pregnenolone is metab-olized to cortisol by sheep adrenal homogenates and by slices of a human adrenal tumor, and the pres-ent authors in preliminary reports have shown th