抗缪勒管激素在硬骨鱼中的一种新型类固醇生成作用:来自欧洲海鲈雄性的证据()。

A Novel Steroidogenic Action of Anti-Müllerian Hormone in Teleosts: Evidence from the European Sea Bass Male ().

作者信息

Mascoli Alessia, Zapater Cinta, Ibañez Soledad, Adolfi Mateus Contar, Schartl Manfred, Gómez Ana

机构信息

Department of Fish Physiology and Biotechnology, Instituto de Acuicultura Torre de la Sal, Consejo Superior de Investigaciones Científicas (CSIC), Torre la Sal, 12595 Castellón, Spain.

Physiological Chemistry, Biocenter, University of Würzburg, 97074 Würzburg, Germany.

出版信息

Int J Mol Sci. 2025 Aug 5;26(15):7554. doi: 10.3390/ijms26157554.

Abstract

The Anti-Müllerian hormone (AMH) is widely recognized for promoting Müllerian duct regression in higher vertebrates and regulating key reproductive functions like steroidogenesis, folliculogenesis, and Leydig cell development. In teleost fish, which lack Müllerian ducts, Amh primarily influences male reproductive functions, including sex determination, testis differentiation, and germ cell proliferation. In adult fish, Amh supports gonad development and spermatogenesis, but its role in teleost gonadal physiology remains largely underexplored. This study reveals a novel steroidogenic function in the European sea bass () using testis culture, plasmid injection, and cell-based transactivation assays. The Amh-induced significant increase in androgen levels was also confirmed in Japanese medaka () treated with recombinant sea bass Amh. Beyond activating the canonical Smad pathway, Amh also triggered the cAMP/PKA signalling pathway via its cognate type II receptor, Amhr2. Inhibitors of these pathways independently and synergistically counteracted Amh-induced CRE-Luc activity, indicating pathway crosstalk. Moreover, inhibition of the cAMP pathway suppressed Amh-induced androgen production in testis cultures, emphasizing the crucial role of protein kinase A in mediating Amh steroidogenic action. These findings uncover a novel steroidogenic function of Amh in teleosts and highlight its broader role in male reproductive physiology.

摘要

抗苗勒管激素(AMH)在高等脊椎动物中促进苗勒管退化以及调节关键生殖功能(如类固醇生成、卵泡发生和睾丸间质细胞发育)方面广为人知。在缺乏苗勒管的硬骨鱼中,Amh主要影响雄性生殖功能,包括性别决定、睾丸分化和生殖细胞增殖。在成年鱼类中,Amh支持性腺发育和精子发生,但其在硬骨鱼性腺生理学中的作用在很大程度上仍未得到充分探索。本研究利用睾丸培养、质粒注射和基于细胞的反式激活分析,揭示了欧洲海鲈()中一种新的类固醇生成功能。在用重组海鲈Amh处理的日本青鳉()中,也证实了Amh诱导雄激素水平显著升高。除了激活经典的Smad途径外,Amh还通过其同源II型受体Amhr2触发cAMP/PKA信号通路。这些途径的抑制剂单独或协同作用可抵消Amh诱导的CRE-Luc活性,表明存在途径间的串扰。此外,抑制cAMP途径可抑制睾丸培养物中Amh诱导的雄激素产生,强调了蛋白激酶A在介导Amh类固醇生成作用中的关键作用。这些发现揭示了硬骨鱼中Amh一种新的类固醇生成功能,并突出了其在雄性生殖生理学中更广泛的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c61b/12347443/e073c36d9cbe/ijms-26-07554-g001.jpg

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