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

Christen M. Anderson, Carole R. Mendelson

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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-450scc) 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-450scc 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 {reversed tilde equals}- 0.25 pmol min-1 mg-1 protein in testes from 19-day fetal rabbits was increased {reversed tilde equals}- 10-fold in testes of 21-day fetuses and thereafter declined dramatically. Immunoreactive cytochrome P-450scc, 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-450scc. 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-450scc. In addition, these data support the hypothesis that the developmental changes in the synthesis of cytochrome P-450scc are regulated by fetal gonadotropin and are mediated by cyclic AMP.

Original languageEnglish (US)
Pages (from-to)121-130
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume55
Issue number2-3
DOIs
StatePublished - Feb 1988

Keywords

  • (Testis
  • Cholesterol side chain cleavage
  • Fetal development
  • Rabbit)
  • Steroidogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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