GLUT1-mediated glycolysis supports GnRH-induced secretion of luteinizing hormone from female gonadotropes.
GLUT1-mediated glycolysis supports GnRH-induced secretion of luteinizing hormone from female gonadotropes.
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GLUT1 介导的糖酵解支持 GnRH 诱导的女性促性腺激素分泌黄体生成素。
DOI：
10.1038/s41598-020-69913-z
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发表时间：
2020
影响因子：
4.6
通讯作者：
Lawson,MarkA
中科院分区：
文献类型：
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作者：
Nicholas,DequinaA;Knight,VashtiS;Tonsfeldt,KarenJ;Terasaka,Tomohiro;Molinar-Inglis,Olivia;Stephens,ShannonBZ;Trejo,JoAnn;Kauffman,AlexanderS;Mellon,PamelaL;Lawson,MarkA
调节生殖抑制以响应营养可用性降低的机制仍不明确，研究表明调节发生在下丘脑、垂体或性腺内。通过在垂体促性腺细胞模型和初级促性腺细胞中操纵葡萄糖利用和GLUT1表达，我们显示了生殖神经肽GnRH对糖酵解的GLUT1依赖性刺激，而不是线粒体呼吸。促性腺激素释放激素刺激增加促性腺激素GLUT1的表达和转移到细胞外膜。促性腺激素促黄体激素的最大分泌由GLUT 1的表达和活性支持，GnRH诱导的糖酵解在初级促性腺激素中重现。GLUT 1表达在体内GnRH诱导的排卵LH峰期间增加，并与GnRHR相关。我们的结论是，垂体前叶的促性腺激素的感觉葡萄糖的可用性和整合这种状态与输入从下丘脑通过GnRH受体信号调节生殖激素的合成和分泌。
The mechanisms mediating suppression of reproduction in response to decreased nutrient availability remain undefined, with studies suggesting regulation occurs within the hypothalamus, pituitary, or gonads. By manipulating glucose utilization and GLUT1 expression in a pituitary gonadotrope cell model and in primary gonadotropes, we show GLUT1-dependent stimulation of glycolysis, but not mitochondrial respiration, by the reproductive neuropeptide GnRH. GnRH stimulation increases gonadotrope GLUT1 expression and translocation to the extracellular membrane. Maximal secretion of the gonadotropin Luteinizing Hormone is supported by GLUT1 expression and activity, and GnRH-induced glycolysis is recapitulated in primary gonadotropes. GLUT1 expression increases in vivo during the GnRH-induced ovulatory LH surge and correlates with GnRHR. We conclude that the gonadotropes of the anterior pituitary sense glucose availability and integrate this status with input from the hypothalamus via GnRH receptor signaling to regulate reproductive hormone synthesis and secretion.