Tamoxifen induces masculinization of genetic females and regulates P450 aromatase and Mullerian inhibiting substance mRNA expression in Japanese flounder (Paralichthys olivaceus)
Tamoxifen induces masculinization of genetic females and regulates P450 aromatase and Mullerian inhibiting substance mRNA expression in Japanese flounder (Paralichthys olivaceus)
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DOI：
10.1002/mrd.20603
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发表时间：
2007-09-01
影响因子：
2.5
通讯作者：
Abe, Shin-Ichi
中科院分区：
文献类型：
--
作者：
Kitano, Takeshi;Yoshinaga, Norifumi;Abe, Shin-Ichi
牙鲆提供了一个很好的模型来阐明性激素在性腺分化中的作用，因为在性分化过程中，性激素处理或水温控制很容易改变性别。我们先前已经证明，高水温、芳香酶抑制剂(法多唑)或17α-甲基睾酮处理会导致遗传雌性牙鲆从遗传雌性向表型雄性的性逆转，并抑制卵巢型P450芳香酶(P450arom)的mRNA表达，P450arom是一种类固醇生成酶，负责雄激素向雌激素的转化。在本研究中，我们证明了用抗雌激素药物(他莫昔芬)治疗遗传性雌鼠可导致其男性化，抑制P450arom基因的表达，并诱导转化生长因子-β(TGF-β)超家族成员苗勒氏抑制物质(MIS)的mRNA表达，而对雌激素受体-oc(ERα)和ERβ的mRNAs表达没有影响。相反，17β-雌二醇抑制了三苯氧胺或高水温处理的遗传雌性小鼠的雄性化，上调了P450arom基因的表达，下调了MISmRNA的表达。这些结果有力地表明，雌激素通过ER信号调节P450arom和MISmRNA的表达，从而显著影响性腺的性别分化。
Japanese flounder, Paralichthys olivaceus, provides an excellent model to elucidate the roles of sex steroid hormones in gonadal sex differentiation because the sex is easily altered by sex steroid treatments or water temperature control during the sex differentiation. We have previously shown that high water temperature, an aromatase inhibitor (fadrozole), or 17 alpha-methyltestosterone treatment causes the sex-reversal from genetic females to phenotypic males and suppression of mRNA expression of ovary-type P450 aromatase (P450arom), which is a steroidogenic enzyme responsible for the conversion of androgens to estrogens, in Japanese flounder. In the present study, we demonstrate that treatment of the genetic females with anti-estrogen (tamoxifen) leads to their masculinization, suppresses P450arom mRNA expression, and induces mRNA expression of Mullerian inhibiting substance (MIS), a member of the transforming growth factor-beta (TGF-beta) superfamily, while it has no effect on mRNAs expression of estrogen receptor-oc (ER alpha) and ER beta. In contrast, 17 beta-estradiol counteracted masculinization of the genetic females by tamoxifen or high water temperature treatment, upregulated P450arom mRNA expression, and downregulated MIS mRNA expression. These results strongly suggest that estrogen signaling through ERs dramatically influences the gonadal sex differentiation by regulating P450arom and MIS mRNA expression.