11-Ketotestosterone Is a Major Androgen Produced in Human Gonads
11-Ketotestosterone Is a Major Androgen Produced in Human Gonads
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DOI：
10.1210/jc.2016-2311
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发表时间：
2016-10-01
影响因子：
5.8
通讯作者：
Yazawa, Takashi
中科院分区：
文献类型：
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作者：
Imamichi, Yoshitaka;Yuhki, Koh-ichi;Yazawa, Takashi
背景：11-酮睾酮（11-KT）是一类新型的活性雄激素。然而，其合成的细节仍然未知human.Objective：本研究的目的是澄清11-KT在human.Design，Participants，和方法：细胞色素P450和11 β-羟基类固醇脱氢酶1型和2型（参与11-KT合成的关键酶）的表达进行了研究在人类性腺。在Leydig细胞中研究了11-KT的产生。在10名女性和10名男性的生育年龄的血浆睾酮和11-KT浓度进行了测量。结果：细胞色素P450和11 β-羟基类固醇脱氢酶1型和2型在睾丸间质细胞和卵泡膜细胞中均有表达。睾丸间质细胞产生11-KT，男性和女性的血浆11-KT水平相对较高。尽管男性的睾酮水平比女性高20倍以上，但11-KT的血浆水平没有性别二型性。值得注意的是，女性的睾酮和11-KT水平相似。在荧光素酶报告系统中，11-KT激活人雄激素受体介导的反式激活。相反，11-KT没有激活雌激素受体介导的反式激活芳香化酶表达的MCF-7细胞，而睾酮转换为雌激素。11-KT不影响雌激素/雌激素受体介导的MCF-7细胞增殖。此外，显着抑制细胞增殖时，雄激素受体转染到MCF-7 cells.Conclusions：目前的研究表明，11-KT是在性腺中产生的，是一种主要的雄激素在人类。它可以潜在地作为一种非芳香化雄激素。
Context: 11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans.Objective: The objective of this study was to clarify the production and properties of 11-KT in human.Design, Participants, and Methods: Expression of cytochrome P450 and 11 beta-hydroxysteroid dehydrogenase types 1 and 2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using breast cancer-derived MCF-7 cells.Results: Cytochrome P450 and 11 beta-hydroxysteroid dehydrogenase types 1 and 2 were detected in Leydig cells and theca cells. Leydig cells produced 11-KT, and relatively high levels of plasma 11-KT were measured in both men and women. There was no sexual dimorphism in the plasma levels of 11-KT, even though testosterone levels were more than 20 times higher in men than in women. It is noteworthy that the levels of testosterone and 11-KT were similar in women. In a luciferase reporter system, 11-KT activated human androgen receptor-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/estrogen receptor -mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when androgen receptor was transfected into MCF-7 cells.Conclusions: The current study indicates that 11-KT is produced in the gonads and represents a major androgen in human. It can potentially serve as a nonaromatizable androgen.