Colocalization of p450c17 and cytochrome b5 in androgen-synthesizing tissues of the human
Colocalization of p450c17 and cytochrome b5 in androgen-synthesizing tissues of the human
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DOI：
10.1095/biolreprod.103.026732
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发表时间：
2004-07-01
影响因子：
3.6
通讯作者：
Parker, CR
中科院分区：
文献类型：
--
作者：
Dharia, S;Slane, A;Parker, CR
雄激素是人体生理的一个组成部分。雄激素的从头产生通常限于肾上腺皮质和性腺。这些类固醇生成组织的雄激素合成需要双功能酶细胞色素P450 c17，其催化17羟化酶和17，20裂解酶活性。17，20-裂解酶活性与雄激素产生的调节有关，并且通过辅助蛋白细胞色素b5（CytB 5）的作用进行变构调节。我们的目的是确定P450 c17和CytB 5在人类雄激素合成组织中的细胞定位。对胎儿和成人肾上腺、卵巢和睾丸进行P450 c17和CytB 5的免疫组织化学分析。在胎儿肾上腺中，CytB 5和P450 c17均见于胎儿区细胞，但在新皮质中未发现。在成人肾上腺中，束状核仅对P450 c17呈免疫反应性，而网状核对P450 c17和CytB 5均呈免疫反应性。在成年性腺中，P450 c17和CytB 5共定位于睾丸间质细胞、卵泡内膜细胞、卵泡膜黄体细胞和卵巢间质中的孤立细胞团。而P450 c17和CytB 5共定位在胎儿睾丸的间质细胞，有没有在妊娠中期胎儿卵巢的免疫染色。CytB 5和P450 c17共定位的研究结果强烈支持CytB 5在胎儿和成人雄激素生物合成途径的调节中起重要作用的观点。
Androgens are an integral part of human physiology. The de novo production of androgens is generally limited to the adrenal cortex and the gonads. Androgen synthesis by these steroidogenic tissues requires the bifunctional enzyme cytochrome P450c17, which catalyzes both 17 hydroxylase and 17,20 lyase activities. 17,20-lyase activity is relevant to the regulation of androgen production, and is allosterically modulated through the action of an accessory protein, cytochrome b5 (CytB5). Our objective was to determine the cellular localization of P450c17 and CytB5 in androgen-synthesizing tissues of the human. Immunohistochemical analyses of P450c17 and CytB5 were performed on fetal and adult human adrenals, ovaries, and testes. In the fetal adrenal, CytB5 and P450c17 were both found in the cells of the fetal zone, but not in the neocortex. In the adult adrenal, the zona fasciculata was immunoreactive for P450c17 only, whereas the zona reticularis was immunopositive for both P450c17 and CytB5. In the adult gonads, P450c17 and CytB5 were colocalized in the Leydig cells of the testis, theca interna cells of the follicle, theca lutein cells, and isolated cell clusters in the ovarian stroma. Whereas P450c17 and CytB5 were colocalized in the Leydig cells of the fetal testes, there was no immunostaining for either in the midgestational fetal ovary. Our findings of colocalization of CytB5 and P450c17 are strongly supportive of the view that CytB5 plays an important role in the regulation of the androgen biosynthetic pathway in the fetal and adult human.