Salian-Mehta Smita, Xu Mei, Pierce Angela, Bliesner Brian, Tobet Stuart, Wierman Margaret E
Departments of Medicine, University of Colorado, School of Medicine, Aurora, CO 80045, USA.
Department of Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA.
Mol Cell Endocrinol. 2014 Aug 5;393(1-2):164-70. doi: 10.1016/j.mce.2014.06.015. Epub 2014 Jun 27.
Prior work has shown the importance of TAM (Tyro3, Axl, Mer) receptor tyrosine kinases in GnRH neuronal development and reproductive function. It is unclear if TAM receptor actions are dependent on ligand activation for their functional effects; thus, we characterized reproductive phenotype of ligand Growth arrest specific gene (Gas6) null mice. Gas6 null mice showed delayed vaginal opening and delayed first estrus. Animals eventually attained normal estrous cycles as adults. The GnRH neuronal population was significantly decreased in Gas6 null adults and embryos, but the final positioning of cell bodies in the hypothalamus was normal. Vaginal tissue showed up-regulation of TAM receptor mRNAs in the absence of the ligand. These data confirm that Gas6 plays a role in early GnRH neuronal development and during vaginal opening. The phenotype of Gas6 KO mice suggests that TAMs function in a ligand-dependent and independent manner to control GnRH neuron development to modulate normal reproductive function.
先前的研究表明，TAM（Tyro3、Axl、Mer）受体酪氨酸激酶在促性腺激素释放激素（GnRH）神经元发育和生殖功能中具有重要作用。目前尚不清楚TAM受体的作用是否依赖配体激活来产生功能效应；因此，我们对配体生长停滞特异性基因（Gas6）缺失小鼠的生殖表型进行了特征分析。Gas6缺失小鼠出现阴道开口延迟和首次发情延迟。这些动物成年后最终达到正常的发情周期。Gas6缺失的成年小鼠和胚胎中GnRH神经元数量显著减少，但下丘脑细胞体的最终定位正常。在缺乏配体的情况下，阴道组织中TAM受体mRNA上调。这些数据证实Gas6在GnRH神经元早期发育和阴道开口过程中发挥作用。Gas6基因敲除小鼠的表型表明，TAM以依赖配体和不依赖配体的方式发挥作用，以控制GnRH神经元发育，从而调节正常生殖功能。
