Melatonin promotes sheep Leydig cell testosterone secretion in a co-culture with Sertoli cells
Melatonin promotes sheep Leydig cell testosterone secretion in a co-culture with Sertoli cells
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DOI：
10.1016/j.theriogenology.2017.10.025
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发表时间：
2018-01-15
期刊：
影响因子：
2.8
通讯作者：
Liu, Yi-Xun
中科院分区：
文献类型：
--
作者：
Deng, Shou-Long;Wang, Zhi-Peng;Liu, Yi-Xun
睾丸间质细胞合成和分泌睾酮，并受支持细胞的调节。这两种细胞类型可能共同调节睾丸雄激素的产生。研究表明，在褪黑素存在的情况下，支持细胞可以显著增强Leydig细胞雄激素的合成，从而调节Leydig和Sertoli细胞的分泌功能。然而，褪黑激素通过支持细胞调节间质细胞雄激素产生的分子机制仍不清楚。在这里，我们发现，10（-7）M褪黑激素增加睾丸激素的生产在共培养Leydig和Sertoli细胞分离绵羊。褪黑激素增加支持细胞中干细胞因子和胰岛素样生长因子-1的表达，减少雌激素的合成。褪黑激素通过膜褪黑激素受体1促进胰岛素样生长因子-1和降低雌激素含量。它还通过视黄酸受体相关孤儿受体α增强干细胞因子表达。加入MEK抑制剂PD 98059，支持细胞培养证明，褪黑激素上调胰岛素样生长因子-1和下调雌激素可能是通过MEK/细胞外信号调节激酶途径。总之，这些结果表明，褪黑激素可能通过调节褪黑激素受体1调节的胰岛素样生长因子-1的表达，以及褪黑激素受体1诱导的抑制雌激素合成，以增加共培养的睾丸间质细胞和支持细胞中的雄激素产生的功能。(C)2017爱思唯尔公司All rights reserved.
Leydig cells synthesize and secrete testosterone, and are regulated by Sertoli cells. These two cell types may work together to regulate testicular androgen production. Studies have shown that Leydig cell androgen synthesis can be dramatically enhanced by Sertoli cells in the presence of melatonin, which can regulate the secretory function of Leydig and Sertoli cells. However, the molecular mechanism of melatonin-regulated Leydig cell androgen production via Sertoli cells remains unclear. Here, we found that 10(-7) M melatonin increased testosterone production in co-cultured Leydig and Sertoli cells isolated from sheep. Melatonin increased the expression of stem cell factor and insulin-like growth factor-1 and decreased estrogen synthesis in Sertoli cells. Melatonin promoted insulin-like growth factor-1 and decreased estrogen content via the membrane melatonin receptor 1. It also enhanced stem cell factor expression via the retinoic acid receptor-related orphan receptor alpha. Addition of PD98059, a MEK inhibitor, to Sertoli cell culture demonstrated that the melatonin upregulation of insulin-like growth factor-1 and downregulation of estrogen may be through the MEK/extracellular signal-regulated kinase pathway. Together, these results suggest that melatonin may function through modulating melatonin receptor 1-regulated insulin-like growth factor-1 expression, as well as melatonin receptor 1-induced suppression of estrogen synthesis to increase androgen production in co-cultured Leydig and Sertoli cells. (C) 2017 Elsevier Inc. All rights reserved.