The Delta-5-3-Beta-Hydroxysteroid Dehydrogenases Of Corpus Luteum And Adrenal .2. Interaction Of C-19 And C-21 Substrates And Products

Incubation of a variety of C 21 -Δ 5 -3β-hydroxy steroids with adrenal and corpus luteum acetone powders in the presence of DBA (3β-hydroxyandrost-5-ene-17-one) resulted in a marked inhibition in the rate of oxidation of the C 21 substrates and preferential oxidation of DHA. DHA-SO 4 was without effect. Androstenedione (androst-4-ene-3,17-dione) was also found not only to inhibit the oxidation of the C 21 -Δ 5 -3β-hydroxysteroids more effectively than DHA, but also inhibited the oxidation of DHA itself. Other Δ 4 -3-ketosterolds such as testosterone (17β-hydroxyandrost-4-ene-17-one) and 11β-hydroxyandrostenedione (11β--hydroxyandrost-4-ene-3, 17-dione) were also found to be effective inhibitors. The inhibition by androstenedione of the C 21 -Δ 5 -3β-hydroxysteroid substrates could not be overcome by increasing the concentration of substrate whereas inhibition of DHA oxidation by androstenedione was clearly competitive for the inhibition could be overcome by increasing the substrate concentration. Progesterone (pregn-4-ene-3,20-dione) was found to be a less potent inhibitor of Δ 5 -3β-ol oxidation, but differed fron androstenedione in that it inhibited the Δ 5 → Δ 4 isomerization step while androstenedione did not. The observed pattern of inhibition and the similarity in relative rates between different tissue preparations suggested the concept of a single enzyme system interacting with the C 21 -Δ 5 -3β-ol substrates whereas the oxidation of the saturated 3β--ol and the Δ 5 -3β-ol, at least for the C 19 substrates, seemed to be mediated by different enzyme systems. Implications of these observations are discussed relative to alteration of steroid biosynthesis in pathologic states of androgen excess and possible roles for the steroid sulfokinases and sulfatases of steroidogenic tissues in the regulation of steroid hormone biosynthesis.