Cortisol induces masculinization of XX medaka through gonadal soma-derived growth factor (GSDF) and anti-Mullerian hormone receptor type 2 (AMHR2)
Cortisol induces masculinization of XX medaka through gonadal soma-derived growth factor (GSDF) and anti-Mullerian hormone receptor type 2 (AMHR2)
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DOI：
10.1007/s12562-020-01479-1
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发表时间：
2020-11-17
影响因子：
1.9
通讯作者：
Kitano, Takeshi
中科院分区：
文献类型：
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作者：
Hara, Seiji;Sawamura, Rie;Kitano, Takeshi
青鳉是一种硬骨鱼，具有与哺乳动物相似的XX/XY性别决定系统。然而，在高温条件下，XX青鳉雄性化的关键硬骨鱼糖皮质激素，皮质醇的升高。皮质醇抑制生殖细胞的雌性型增殖，并诱导XX青鳉性腺性别分化过程中的雄性化。为了确定皮质醇下游的雄性化机制，我们分析了性腺体源性生长因子（gsdf）和抗苗勒管激素受体2型（amhr 2）的功能，这些基因被认为在抑制生殖细胞增殖和雄性分化中发挥重要作用。我们使用gsdf敲除（KO）和amhr 2 KO青鳉研究了gsdf和amhr 2对生殖细胞增殖的影响。在孵化阶段，gsdf或amhr 2功能的丧失恢复了皮质醇处理下生殖细胞的雌性型增殖。此外，皮质醇处理gsdf KO或amhr 2 KO青鳉没有诱导XX青鳉雄性化。这些结果表明，皮质醇抑制生殖细胞的雌性型增殖，并通过GSDF和AMHR 2诱导XX青鳉的雄性化。因此，这项研究提供了第一个证据表明，GSDF和AMHR 2参与皮质醇诱导的男性化。
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-Mullerian 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.