Sequential Biotransformation of 5-Pregnenolone-7α-3H and Progesterone-4-14C Into Androgens by Mouse Testes

Abstract

The sequential biotransformation of 5-pregnenolone-7α-³H and progesterone- 4-¹⁴C into testosterone was ascertained for mouse testicular tissue in vitro. In this respect, 5-pregnenolone-7α-³H was converted into progesterone, 17α-hydroxyprogesterone, and androstenedione. Similarly, progesterone-4-MC was converted into these compounds at a rate paralleling that of 5- pregnenolone-7α-³H. However, there was a much more rapid accumulation of ³H-labeled steroid in the testosterone steroid fraction than was observed for ¹⁴C-labeled steroid. These data indicate that an alternate pathway exists for the biotransformation of 5-pregnenolone into testosterone with an initial rate faster than that observed for progesterone. This alternate route was postulated as going through 17α-hydroxypregnenolone, dehydroepiandrostenedione and 5-androstenediol. After approximately 90 to 120 min of incubation, there was an increase in the ³H- and ¹⁴C- labeled steroid content of the androstenedione and 17α-hydroxyprogesterone steroid pools. This increase was observed even though the radioactive labeled steroid content of the progesterone steroid pool remained low during this period. The increase in the 17α-hydroxyprogesterone and androstenedione steroid pools after approximately 90 to 120 min of incubation was attributed to the conversion of 17α,20α- and 17α,20β-dihydroxyprogesterone into 17α-hydroxyprogesterone and the subsequent conversion of 17α-hydroxyprogesterone into androstenedione. (Endocrinology76: 591, 1965)