Anderson C M, Mendelson C R
Department of Biochemistry, University of Texas Health Science Center, Dallas 75235.
Mol Cell Endocrinol. 1988 Feb;55(2-3):121-30. doi: 10.1016/0303-7207(88)90126-8.
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 approximately equal to 0.25 pmol min-1 mg-1 protein in testes from 19-day fetal rabbits was increased approximately equal to 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.
雄性性分化取决于胎儿睾丸在发育关键阶段诱导睾酮合成。在兔子中，胎儿睾丸的睾酮合成在妊娠17.5 - 18天后开始，在第21天达到峰值，随后下降。在本研究中，我们分析了发育过程中胎儿兔睾丸中免疫反应性胆固醇侧链裂解细胞色素P - 450（细胞色素P - 450scc）的比活性和浓度，以评估其作为胎儿睾丸类固醇生成关键调节酶的可能作用。还评估了人绒毛膜促性腺激素（hCG）和二丁酰环磷腺苷对体外培养的胎儿兔睾丸中细胞色素P - 450scc比活性和合成的影响。我们观察到胆固醇侧链裂解活性的变化与睾酮合成的诱导平行；该酶在19天胎儿兔睾丸中的比活性约为0.25 pmol min⁻¹ mg⁻¹蛋白质，在21天胎儿的睾丸中增加了约10倍，此后急剧下降。免疫反应性细胞色素P - 450scc在19天胎儿兔性腺中首次可检测到，在21天胎儿睾丸中显著诱导，在第24天达到最高水平，此后略有下降。将19天和21天胎龄胎儿兔的睾丸与hCG或二丁酰环磷腺苷孵育24小时导致睾酮合成、胆固醇侧链裂解活性和细胞色素P - 450scc合成的诱导。这些发现表明胎儿睾丸间质细胞的雄激素合成是由细胞色素P - 450scc合成和比活性的诱导介导的。此外，这些数据支持细胞色素P - 450scc合成的发育变化受胎儿促性腺激素调节并由环磷腺苷介导的假设。
