The medaka Oryzias latipes is a teleost fish with an XX/XY sex determination system similar to that of mammals. However, under high-temperature conditions, XX medaka are masculinized by an elevation of the key teleost glucocorticoid, cortisol. Cortisol inhibits female-type proliferation of germ cells and induces masculinization of XX medaka during gonadal sex differentiation. To identify masculinization mechanisms downstream of cortisol, we analysed the functions of gonadal soma-derived growth factor ( gsdf ) and anti-Müllerian hormone receptor type 2 ( amhr2 ); these genes are known to play important roles in the inhibition of germ cell proliferation and male differentiation. We investigated the impact of gsdf and amhr2 on the proliferation of germ cells using gsdf knockout (KO) and amhr2 KO medaka. At hatching stage, loss of gsdf or amhr2 function recovered female-type proliferation in germ cells under cortisol treatment. Moreover, cortisol treatment of gsdf KO or amhr2 KO medaka did not induce masculinization of XX medaka. These results suggest that cortisol inhibits female-type proliferation of germ cells and induces masculinization of XX medaka through GSDF and AMHR2. This study thereby provides the first evidence that GSDF and AMHR2 are involved in cortisol-induced masculinization.

中文翻译：

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皮质醇通过性腺体细胞衍生生长因子 (GSDF) 和抗苗勒管激素受体 2 型 (AMHR2) 诱导 XX 鳉的男性化

青鳉是一种硬骨鱼，其 XX/XY 性别决定系统类似于哺乳动物。然而，在高温条件下，XX 鳉由于关键硬骨鱼糖皮质激素皮质醇的升高而男性化。皮质醇抑制生殖细胞的女性型增殖，并在性腺性别分化过程中诱导 XX 鳉的男性化。为了确定皮质醇下游的男性化机制，我们分析了性腺体细胞衍生生长因子 ( gsdf ) 和抗苗勒管激素受体 2 型 ( amhr2 ) 的功能；已知这些基因在抑制生殖细胞增殖和雄性分化方面发挥重要作用。我们使用 gsdf 敲除 (KO) 和 amhr2 KO medaka 研究了 gsdf 和 amhr2 对生殖细胞增殖的影响。在孵化阶段，在皮质醇处理下，gsdf 或 amhr2 功能的丧失恢复了生殖细胞中的女性型增殖。此外，gsdf KO 或 amhr2 KO medaka 的皮质醇处理不会诱导 XX medaka 的男性化。这些结果表明皮质醇抑制生殖细胞的女性型增殖并通过 GSDF 和 AMHR2 诱导 XX 鳉的男性化。因此，这项研究提供了第一个证据，证明 GSDF 和 AMHR2 参与了皮质醇诱导的男性化。