METABOLISM OF 3β-HYDROXY-Δ5- AND 3-OXO-Δ4-C19 AND C21 STEROIDS IN HUMAN LIVER MICROSOMES

Abstract

ABSTRACT The metabolism of [4-14C] dehydroepiandrosterone*, [4-14C] pregnenolone, [4-14C] androstenedione, [4-14C] testosterone and [4-14C] progesterone in microsomal preparations of human liver has been studied. [4-14C] Dehydroepiandrosterone with NADPH as cofactor gave the following composition of products: 3β,7β-dihydroxy-5-androsten-17-one (about 25%), 3β-hydroxy-5-androstene-7,17-dione (about 25%), 3β,7α-dihydroxy-5-androsten-17-one (about 10%), 3β,17β-dihydroxy-5-androsten16-one (about 10%), 6β-hydroxy-4-androstene-3,17-dione (about 10%), 3β,16α-dihydroxy-5-androsten-17-one (< 5%), 5-androstene-3β,16α,17β-triol (< 5%) and 6α-hydroxy-4-androstene-3,17-dione (< 5%). In addition an unidentified hydroxylated derivative of dehydroepiandrosterone (about 10%) was formed. [4-14C] Dehydroepiandrosterone with NAD as cofactor was converted into androstenedione. [4-14C] Pregnenolone with NADPH as cofactor was metabolized only to a small degree, and of the products formed, only 6β-hydroxy-4-pregnene-3,20-dione (about 20% of products) and 3β,16α-dihydroxy-5-pregnen-20-one (about 10% of products) could be identified. Pregnenolone with NAD as cofactor was converted into progesterone. [4-14C] Testosterone with NADPH as cofactor gave the following composition of products: 6β,17β-dihydroxy-4-androsten-3-one (30–50%), androstenedione (25–40%), 2ε,17β-dihydroxy-4-androsten-3-one (5–10%), 6β-hydroxy-4-androstene-3,17-dione (about 5%), 1β,17β-dihydroxy-4-androsten-3-one (< 5%), 15β,17β-dihydroxy-4-androsten-3-one (< 5%) and 16α,17β-dihydroxy-4-androsten-3-one (< 5%). [4-14C] Androstenedione with NADPH as cofactor gave the following composition of products: 6β-hydroxy-4-androstene-3,17-dione (50–60%), 5α-androstane-3,17-dione (about 10%), testosterone (about 5%), 17β-hydroxy-4-androstene-3,16-dione (about 5%) and 3β-hydroxy-5α-androstan-17-one (about 5%). [4-14C] Progesterone with NADPH as cofactor gave the following composition of products: 6β-hydroxy-4-pregnene-3,20-dione (about 30%), 5α-pregnane-3,20-dione (10–20%), 3β-hydroxy-5-pregnan-20-one (about 10%) and 6α-hydroxy-4-pregnene-3,20-dione (5%).