Developmental and hormonal regulation of cholesterol side chain cleavage cytochrome P-450 in the fetal rabbit testis

Abstract

Male sexual differentiation is dependent upon the induction of testosterone synthesis by the fetal testis at a critical phase of development. In the rabbit, testosterone synthesis by the fetal testis is initiated after 17.5–18 days of gestation, reaches peak values by day 21 and subsequently declines. In the present study, we analyzed the specific activity and concentration of immunoreactive cholesterol side chain cleavage cytochrome P-450 (cytochrome P-450 scc) in the fetal rabbit testis during development to assess its possible role as a key regulatory enzyme in fetal testicular Steroidogenesis. The effects of human chorionic gonadotropin (hCG) and dibutyryl cyclic AMP on the specific activity and synthesis of cytochrome P-450 scc in fetal rabbit testes in vitro also were evaluated. We observed that changes in cholesterol side chain cleavage activity paralleled the induction of testosterone synthesis; the specific activity of this enzyme which was ⋍- 0.25 pmol min −1 mg −1 protein in testes from 19-day fetal rabbits was increased ⋍- 10-fold in testes of 21-day fetuses and thereafter declined dramatically. Immunoreactive cytochrome P-450 scc, which was first detectable in gonads of 19-day fetal rabbits, was induced markedly in 21-day fetal testes, reached maximum levels on day 24 and declined slightly thereafter. Incubation of testes from 19-and 21-day gestational age fetal rabbits with hCG or dibutyryl cyclic AMP for 24 h resulted in an induction of testosterone synthesis, cholesterol side chain cleavage activity and synthesis of cytochrome P-450 scc. These findings are suggestive that androgen synthesis by the fetal Leydig cell is mediated by an induction of the synthesis and specific activity of cytochrome P-450 scc. In addition, these data support the hypothesis that the developmental changes in the synthesis of cytochrome P-450 scc are regulated by fetal gonadotropin and are mediated by cyclic AMP.