Liu Yun, Tang Haipei, Xie Rui, Li Shuisheng, Liu Xiaochun, Lin Haoran, Zhang Yong, Cheng Christopher H K
State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals, and the Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.
School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Endocrinology. 2017 Mar 1;158(3):604-611. doi: 10.1210/en.2016-1540.
It is generally believed that kisspeptin and gonadotropin-releasing hormone (GnRH) are required for reproduction in vertebrates. In this study, we generated gnrh3-null zebrafish and found that gnrh3 mutation did not impair gonad development and reproductive capacity. Moreover, zebrafish triple knockout mutant lacking gnrh3 and the 2 kiss1s genes undergo normal puberty and gonad maturation. The expression of follicle-stimulating hormone beta (fshβ) and luteinizing hormone beta (lhβ) was not significantly altered whereas the expression of neuropeptide Y (npy), tachykinin 3 (tac3), and secretogranin-II (sgII) was significantly increased in the triple knockout mutant, suggesting that compensation mechanisms exist to stimulate the reproductive axis in the absence of kiss and gnrh. Our results challenge the prevailing view that GnRH is indispensable for reproduction across species. These data provide genetic evidence that different mechanisms have evolved for the neuroendocrine control of reproduction between mammals and fish: pulsatile release of GnRH to the portal system is the final gateway to stimulate the reproductive axis in mammals, whereas multiple factors act in parallel with GnRH to stimulate the reproductive axis in certain fish species.
一般认为，在脊椎动物中， kisspeptin和促性腺激素释放激素（GnRH）是繁殖所必需的。在本研究中，我们构建了gnrh3基因敲除的斑马鱼，发现gnrh3突变并不损害性腺发育和繁殖能力。此外，缺乏gnrh3和两个kiss1基因的斑马鱼三重敲除突变体经历正常的青春期和性腺成熟。三重敲除突变体中促卵泡激素β（fshβ）和促黄体生成素β（lhβ）的表达没有显著改变，而神经肽Y（npy）、速激肽3（tac3）和分泌粒蛋白II（sgII）的表达显著增加，这表明在缺乏kiss和gnrh的情况下存在补偿机制来刺激生殖轴。我们的结果挑战了GnRH对所有物种繁殖都不可或缺的主流观点。这些数据提供了遗传学证据，表明哺乳动物和鱼类在神经内分泌对繁殖的控制方面进化出了不同的机制：GnRH向门脉系统的脉冲式释放是刺激哺乳动物生殖轴的最终途径，而在某些鱼类物种中，多种因素与GnRH并行作用以刺激生殖轴。
