Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: conservation and evolution of the androgen metabolic pathway.
Cyp11b1 is induced in the murine gonad by luteinizing hormone/human chorionic gonadotropin and involved in the production of 11-ketotestosterone, a major fish androgen: conservation and evolution of the androgen metabolic pathway.
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DOI：
10.1210/en.2007-1015
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发表时间：
2008-04
期刊：
影响因子：
4.8
通讯作者：
T. Yazawa;Miki Uesaka;Y. Inaoka;T. Mizutani;T. Sekiguchi;Takashi Kajitani;T. Kitano;A. Umezawa;K. Miyamoto
中科院分区：
文献类型：
--
作者：
T. Yazawa;Miki Uesaka;Y. Inaoka;T. Mizutani;T. Sekiguchi;Takashi Kajitani;T. Kitano;A. Umezawa;K. Miyamoto
我们以前已经表明，Cyp 11b 1，一种负责肾上腺糖皮质激素生物合成的11 β-羟化酶，在来自间充质干细胞的产生雄激素的Leydig样细胞中被cAMP诱导。我们发现，Cyp 11b 1诱导雄性Leydig细胞，或女性卵泡膜细胞，当人绒毛膜促性腺激素在未成熟的小鼠。Cyp 11b 1基因在啮齿类动物性腺中的表达导致了11-酮睾酮（11-KT）的产生，11-KT是一种主要的鱼类雄激素，可诱导鱼类的雄性分化或精子发生。在硬骨鱼，11-KT的血浆浓度升高，在人绒毛膜促性腺激素治疗的小鼠。然而，与硬骨鱼相反，尽管雄性小鼠的睾酮（前体底物）水平高出约20倍，但11-KT的血浆浓度在两性中相似。由于11 β-羟类固醇脱氢酶2型在小鼠卵巢中的表达比睾丸中高得多，因此睾酮转化为11-KT可能在卵巢中更有效地发生。在对雄激素有反应并被雄激素激活的荧光素酶报告系统中，11-KT有效地激活了哺乳动物雄激素受体介导的反式激活。我们的研究结果表明，雄激素代谢途径是保守的硬骨鱼和哺乳动物之间，尽管性优势和生殖功能的11-KT在进化过程中被改变。
We have shown previously that Cyp11b1, an 11beta-hydroxylase responsible for glucocorticoid biosynthesis in the adrenal gland, was induced by cAMP in androgen-producing Leydig-like cells derived from mesenchymal stem cells. We found that Cyp11b1 was induced in male Leydig cells, or female theca cells, when human chorionic gonadotropin was administered in immature mice. Expression of Cyp11b1 in rodent gonads caused the production of 11-ketotestosterone (11-KT), a major fish androgen, which induces male differentiation or spermatogenesis in fish. As in teleosts, plasma concentrations of 11-KT were elevated in human chorionic gonadotropin-treated mice. In contrast to teleosts, however, plasma concentrations of 11-KT were similar in both sexes, despite levels of testosterone, a precursor substrate, being about 20 times higher in male mice. Because expression of 11beta-hydroxysteroid dehydrogenase type 2, was much higher in the mouse ovary than in the testis, conversion of testosterone into 11-KT may occur more efficiently in the ovary. In a luciferase reporter system that was responsive to and activated by androgens, 11-KT efficiently activated mammalian androgen receptor-mediated transactivation. Our results suggest that the androgen metabolic pathway is conserved between teleosts and mammals, despite sexual dominance and reproductive functions of 11-KT being altered during evolution.