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人类胎儿中甾体生成酶P450scc(20,22-碳链裂解酶)、P450c17(17α-羟化酶/17,20-裂解酶)和P450c21(21-羟化酶)基因的发育表达。

Developmental expression of genes for the stereoidogenic enzymes P450scc (20,22-desmolase), P450c17 (17 alpha-hydroxylase/17,20-lyase), and P450c21 (21-hydroxylase) in the human fetus.

作者信息

Voutilainen R, Miller W L

出版信息

J Clin Endocrinol Metab. 1986 Nov;63(5):1145-50. doi: 10.1210/jcem-63-5-1145.

DOI:10.1210/jcem-63-5-1145
PMID:3489728
Abstract

Fetal adrenal steroidogenesis is required for the production of placental estrogen, and fetal testicular steroidogenesis is required for the development of male external genitalia. We studied the ontogeny and tissue specificity of expression of the genes for three steroidogenic enzymes: P450scc (the cholesterol side-chain cleavage enzyme), P450c17 (17 alpha-hydroxylase/17,20-lyase), and P450c21 (21-hydroxylase) in the human fetus. RNA from fetal tissues was probed with homologous human P450scc, P450c17, and P450c21 cDNAs cloned in our laboratory. At 20-21 weeks gestation, P450scc mRNA was most abundant in the adrenal, followed by testis, placenta, and ovary. P450c17 mRNA was also most abundant in the adrenal, followed by testis and ovary, but was undetectable in the placenta. P450c21 mRNA was detected only in the adrenal. None of these mRNAs was detected in kidney, liver, spleen, intestine, or muscle. Twenty-two fetal testis samples (13-25.8 weeks gestation) were studied. P450scc and P450c17 mRNAs were most abundant at 14-16 weeks and diminished to 35 and 19% of their peak values, respectively, by 20-25.8 weeks. Ovarian P450scc and P450c17 mRNAs were present, respectively, in only 6.2% and 1.8% of the maximum amount in the testis and did not vary detectably from 14.9 to 21.5 weeks gestation. The testicular and ovarian steroidogenic enzyme mRNA data correlate well with previously reported changes in gonadal steroidogenesis with gestational age. The presence of P450scc mRNA, but not P450c17 mRNA, in the placenta indicates that the placenta is able to initiate the synthesis of some steroid hormones, but is not able to synthesize estrogen de novo. Since P450c21 was found only in the adrenal, the extraadrenal 21-hydroxylation of progesterone to deoxycorticosterone, a common event in the fetus, is probably mediated by an enzyme(s) other than P450c21.

摘要

胎盘雌激素的产生需要胎儿肾上腺类固醇生成,而男性外生殖器的发育需要胎儿睾丸类固醇生成。我们研究了三种类固醇生成酶基因的个体发生及组织特异性表达:P450scc(胆固醇侧链裂解酶)、P450c17(17α-羟化酶/17,20-裂解酶)和P450c21(21-羟化酶)在人类胎儿中的表达情况。用我们实验室克隆的同源人类P450scc、P450c17和P450c21 cDNA对胎儿组织的RNA进行检测。妊娠20 - 21周时,P450scc mRNA在肾上腺中含量最高,其次是睾丸、胎盘和卵巢。P450c17 mRNA在肾上腺中也含量最高,其次是睾丸和卵巢,但在胎盘中未检测到。P450c21 mRNA仅在肾上腺中检测到。在肾脏、肝脏、脾脏、肠道或肌肉中均未检测到这些mRNA。对22份胎儿睾丸样本(妊娠13 - 25.8周)进行了研究。P450scc和P450c17 mRNA在14 - 16周时含量最高,到20 - 25.8周时分别降至峰值的35%和19%。卵巢中的P450scc和P450c17 mRNA分别仅为睾丸中最大量的6.2%和1.8%,在妊娠14.9至21.5周期间未检测到明显变化。睾丸和卵巢类固醇生成酶mRNA数据与先前报道的性腺类固醇生成随胎龄的变化情况高度相关。胎盘中存在P450scc mRNA,但不存在P450c17 mRNA,这表明胎盘能够启动某些类固醇激素的合成,但不能从头合成雌激素。由于仅在肾上腺中发现了P450c21,胎儿中常见的孕酮经肾上腺外21-羟化生成脱氧皮质酮的过程可能由P450c21以外的一种或多种酶介导。

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