Ontogeny of expression of the genes for steroidogenic enzymes P450 side-chain cleavage, 3 beta-hydroxysteroid dehydrogenase, P450 17 alpha-hydroxylase/C17-20 lyase, and P450 aromatase in fetal mouse gonads.

Ontogeny of expression of the genes for steroidogenic enzymes P450 side-chain cleavage, 3 beta-hydroxysteroid dehydrogenase, P450 17 alpha-hydroxylase/C17-20 lyase, and P450 aromatase in fetal mouse gonads.
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DOI:
10.1210/endo.135.1.8013361
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发表时间:
1994-07
期刊:
影响因子:
4.8
通讯作者:
Tamara L. Greco;Anita H. Payne
Tamara L. Greco;Anita H. Payne
中科院分区:
医学2区
文献类型:
--
作者:
Tamara L. Greco;Anita H. Payne

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众所周知,胎儿雄激素是男性性分化所必需的,并且认为胎儿卵巢不具有类固醇生成活性。然而,分子的细节,如类固醇生成酶存在于胎儿睾丸和酶缺乏胎儿卵巢,尚未建立。在小鼠性腺的胚胎发育过程中,研究了编码雄激素和雌激素产生所需的四种类固醇生成酶的基因的表达模式。胆固醇侧链裂解(P450 SCC)、3 β-羟基类固醇脱氢酶/δ 5-δ 4-异构酶的信使RNA(mRNA)表达(3 β HSD)、P450 17 α-羟化酶/C17-20裂解酶(P450 c17)和P450芳香化酶(P450 arom)在卵巢和睾丸区分之前测定(13天后的概念)和性别分化(15,17,和20天后的概念)使用逆转录酶-聚合酶链反应(RT-PCR)。在第13天使用Sry的PCR测定来确定性别。P450 SCC,3 β HSD,和P450 C17转录检测在所有年龄的胎儿睾丸,表明mRNA的类固醇生成酶,需要胆固醇转化为雄激素存在于男性性腺,甚至在性别分化。P450 arom mRNA在第17天在几个胎儿睾丸中检测到,但在第20天一直观察到。P450 arom的表达提示胎儿和新生儿睾丸有将雄激素转化为雌激素的潜力。相比之下,虽然3 β HSD mRNA在几个卵巢检测,P450 SCC,P450 C17和P450 arom转录检测是罕见的。这些数据表明,胎儿卵巢类固醇激素生产的缺乏是缺乏至少三种类固醇生成酶,P450 SCC,P450 c17和P450 arom的表达的结果。
It is well known that fetal androgens are required for male sexual differentiation, and it is thought that fetal ovaries are not steroidogenically active. However, molecular details, such as which steroidogenic enzymes are present in fetal testes and which enzymes are absent in fetal ovaries, have not been established. The pattern of expression of the genes that encode four of the steroidogenic enzymes necessary for androgen and estrogen production was examined during fetal development in mouse gonads. Messenger RNA (mRNA) expression for cholesterol side-chain cleavage (P450scc), 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase (3 beta HSD), P450 17 alpha-hydroxylase/C17-20 lyase (P450c17), and P450 aromatase (P450arom) was determined before ovaries and testes were distinguishable (13 days postconception) and during sexual differentiation (15, 17, and 20 days postconception) using reverse transcriptase-polymerase chain reactions (RT-PCR). A PCR assay for Sry was used to determine gender on day 13. P450scc, 3 beta HSD, and P450c17 transcripts were detected at all ages in fetal testes, indicating that mRNAs for the steroidogenic enzymes that are required to convert cholesterol to androgens are present in the male gonad even before sexual differentiation. P450arom mRNA was detected in several fetal testes on day 17, but consistently observed on day 20. The expression of P450arom suggests the potential of fetal and neonatal testes to convert androgens to estrogens. In contrast, although 3 beta HSD mRNA was detected in several of the ovaries examined, the detection of P450scc, P450c17, and P450arom transcripts was rare. These data suggest that the absence of fetal ovarian steroid hormone production is the result of lack of expression of at least three of the steroidogenic enzymes, P450scc, P450c17, and P450arom.