Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto, Japan.
Endocrinology. 2010 Aug;151(8):3900-8. doi: 10.1210/en.2010-0228. Epub 2010 Jun 9.
In vertebrates, sex is normally determined by genotype. However, in poikilothermal vertebrates, including reptiles, amphibians, and fishes, sex determination is greatly influenced by environmental factors, such as temperature. Little is known about the molecular mechanisms underlying environmental sex determination in these species. The Japanese flounder (Paralichthys olivaceus) is a teleost fish with an XX/XY sex determination system. However, XX flounder can be induced to develop into predominantly either phenotypic females or males, by rearing at 18 or 27 C, respectively, during the sex differentiation period. Therefore, the flounder provides an excellent model to study the molecular mechanisms underlying temperature-dependent sex determination. We previously showed that an aromatase inhibitor, an antiestrogen, and 27 C treatments cause masculinization of XX flounder, as well as suppression of mRNA expression of ovary-type aromatase (cyp19a1), a steroidogenic enzyme responsible for the conversion of androgens to estrogens in the gonads. Furthermore, estrogen administration completely inhibits masculinization by these treatments, suggesting suppression of cyp19a1 mRNA expression, and the resultant estrogen biosynthesis may trigger masculinization of the XX flounder induced by high water temperature. Here, we demonstrated that cortisol causes female-to-male sex reversal by directly suppressing cyp19a1 mRNA expression via interference with cAMP-mediated activation and that metyrapone (an inhibitor of cortisol synthesis) inhibits 27 C-induced masculinization of XX flounder. Moreover, cortisol concentrations in 27 C-reared juveniles were significantly higher than in 18 C-reared fishes during sexual differentiation. These results strongly suggest that masculinization by high water temperature is ascribable to elevation of cortisol concentration during gonadal sex differentiation in the flounder.
在脊椎动物中，性别通常由基因型决定。然而，在变温脊椎动物中，包括爬行动物、两栖动物和鱼类，性别决定受环境因素的影响很大，如温度。关于这些物种环境性别决定的分子机制知之甚少。日本牙鲆（Paralichthys olivaceus）是一种具有 XX/XY 性别决定系统的硬骨鱼。然而，通过在性别分化期分别在 18°C 或 27°C 下饲养，可以将 XX 牙鲆诱导发育为主要的表型雌性或雄性。因此，牙鲆为研究温度依赖性性别决定的分子机制提供了一个极好的模型。我们之前曾表明，芳香酶抑制剂（一种抗雌激素）和 27°C 处理会导致 XX 牙鲆的雄性化，并抑制卵巢型芳香酶（cyp19a1）的 mRNA 表达，该酶是一种甾体生成酶，负责将雄激素转化为性腺中的雌激素。此外，雌激素的给药完全抑制了这些处理引起的雄性化，表明 cyp19a1 mRNA 表达的抑制，以及由此产生的雌激素生物合成可能触发由高温水诱导的 XX 牙鲆的雄性化。在这里，我们证明皮质醇通过直接抑制 cyp19a1 mRNA 表达来导致雌性到雄性的性别反转，通过干扰 cAMP 介导的激活，并且美替拉酮（皮质醇合成的抑制剂）抑制 XX 牙鲆在 27°C 下诱导的雄性化。此外，在性别分化期间，27°C 培养的幼鱼中的皮质醇浓度明显高于 18°C 培养的鱼类。这些结果强烈表明，高温水引起的雄性化归因于在牙鲆的性腺性别分化期间皮质醇浓度的升高。
