BIOSYNTHESIS OF C19 STEROIDS FROM 4-14C-CHOLESTEROL AND 7-3H-PREGNENOLONE IN VIVO: CONSIDERATION OF NEW PATHWAYS

Abstract

3H and 14C specific activities of dehydroepiandrosterone, androsterone, 3[alpha]-hydroxy-5[beta]-androstan-17-one and 3[alpha]-hydroxy-5[alpha]-androst-16-ene (without dilution) have been determined following a single intravenous injection of 4-14C-cholesterol and 7[alpha]-3H-pregnenolone to a virilized woman with an adrenal adenoma and massive dehydroepiandrosterone excretion. Assuming a one compartment model, or a two compartment model in which the injected radioactivity enters the compartment in which the precursor is secreted exclusively, a new pathway by which dehydroepiandrosterone is formed from cholesterol not through preg-nenolone and possibly by cleavage of the side chain C-17 and C-20 is indicated. Analysis of the data by a model in which pregnenolone is secreted into two separate compartments in which progesterone and dehydroepiandrosterone are made, respectively, would explain the findings without necessitating the assumption of a new pathway. 3[alpha]-Hydroxy-5[alpha]-androst-16-ene was isolated from urine following incubation with [beta]-glucuronidase and partition chromatography on celite suggesting that this steroid is a genuine natural product as surmised by Prelog & Ruzicka (1944) and Brooksbank & Haslewood (1950). 2-14C-Mevalonate was shown to give rise to C19 steroids which is the first in vivo demonstration that mevalonic acid is a precursor of the steroid nucleus in man.