The SET protein promotes androgen production in testicular Leydig cells.
The SET protein promotes androgen production in testicular Leydig cells.
复制标题
SET 蛋白促进睾丸 Leydig 细胞中雄激素的产生。
作者：
Zhang B;Ma W;Zhu Q;Xu W;Gao L;Xu B;Xu S;Gao C;Gao L;Liu J;Cui Y
大约40%的中年男性表现出迟发性性腺功能减退症（洛）的症状。然而，雄激素缺乏的机制目前仍不清楚。如我们以前的研究所示，SET蛋白在睾丸间质细胞和卵巢颗粒细胞中表达。本研究旨在探讨SET蛋白对睾丸间质细胞雄激素产生的影响。将AdCMV/SET和AdH 1 siRNA/SET腺病毒分别转导至体外培养的小鼠Leydig细胞系（mLTC-1）中，同时进行或不进行人绒毛膜促性腺激素（HCG）刺激。原代小鼠Leydig细胞用于确认mLTC-1细胞的主要数据。SET蛋白在mLTC-1细胞的细胞质和细胞核中表达。与对照组相比，在过表达SET蛋白的mLTC-1细胞中睾酮的产生显著增加（p < 0.05），而在SET敲低的mLTC-1细胞中睾酮的产生显著降低（p < 0.05）。与睾酮水平一致，类固醇生成急性调节（星星）和细胞色素P450 c17 α-羟化酶（CYP 17 a1）mRNA和蛋白的表达水平根据SET蛋白的表达水平同步变化。有趣的是，在用0.04和0.1 U/mL hCG刺激的mLTC-1细胞中，SET蛋白的表达显著增加。在用AdH 1 siRNA/SET转染并同时用0.1 U/mL hCG刺激的mLTC-1细胞中，睾酮产生和星星表达均显著低于未敲除SET的细胞（p < 0.05）。结论：SET蛋白通过增加星星和CYP 17 a1的表达参与调节睾酮的产生，可能是经典的促黄体生成激素（LH）/促黄体生成激素受体（LHR）信号通路的下游因子。本研究有助于我们对睾丸激素合成的细胞内机制和老年男性洛缺失的病理生理机制的理解。
Approximately 40% of middle‐aged men exhibit symptoms of late‐onset hypogonadism (LOH). However, the mechanism of androgen deficiency is still currently unclear. As shown in our previous studies, the SET protein is expressed in testicular Leydig cells and ovarian granule cells. This study was designed to investigate the effect of the SET protein on androgen production in Leydig cells. The AdCMV/SET and AdH1siRNA/SET adenoviruses were individually transduced into a cultured mouse Leydig cell line (mLTC‐1) with or without human chorionic gonadotropin (HCG) stimulation in vitro. The primary mouse Leydig cells were used to confirm the main data from mLTC‐1 cells. The SET protein was expressed in the cytoplasm and nucleus of mLTC‐1 cells. Testosterone production was significantly increased in mLTC‐1 cells overexpressing the SET protein compared with the control group (p < 0.05), whereas testosterone production was significantly decreased in the SET knockdown mLTC‐1 cells (p < 0.05). Consistent with the testosterone levels, the expression levels of the steroidogenic acute regulatory (StAR) and cytochrome P450c17α‐hydroxylase (CYP17a1) mRNAs and proteins synchronously changed according to the expression level of the SET protein. Interestingly, the expression of the SET protein was significantly increased in the mLTC‐1 cells stimulated with 0.04 and 0.1 U/mL hCG. In the mLTC‐1 cells transfected with AdH1siRNA/SET and concurrently stimulated with 0.1 U/mL hCG, both testosterone production and StAR expression were significantly lower than in the cells without SET knockdown (p < 0.05). In conclusion, the SET protein participates in regulating testosterone production by increasing the expression of StAR and CYP17a1, and it may be a downstream factor of the classic luteinizing hormone (LH)/luteinizing hormone receptor (LHR) signaling pathway. This study improves our understanding of the intracellular mechanism of testicular steroidogenesis and the pathophysiological mechanism of LOH in the aging male.
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影响因子：
2.8
作者：
Boqun X;Xiaonan D;Yugui C;Lingling G;Xue D;Gao C;Feiyang D;Jiayin L;Gao L;Li M;Zhang Y;Ma X
通讯作者：
Ma X
影响因子：
--
作者：
Compagnone, NA;Zhang, P;Mellon, SH
通讯作者：
Mellon, SH
影响因子：
64.5
作者：
Seo, SB;McNamara, P;Chakravarti, D
通讯作者：
Chakravarti, D
影响因子：
4.8
作者：
Li, M;Makkinje, A;Damuni, Z
通讯作者：
Damuni, Z
影响因子：
3.5
作者：
Shen, CX;Buck, AK;Reske, SN
通讯作者：
Reske, SN