The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway
The adiponectin paralog C1q/TNF-related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway
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DOI：
10.1016/j.cyto.2012.01.018
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发表时间：
2012-05-01
期刊：
影响因子：
3.8
通讯作者：
Maeda, Takashi
中科院分区：
文献类型：
--
作者：
Otani, Masataka;Kogo, Mikihiko;Maeda, Takashi
CTRP 3是脂联素的一个副产物，是C1 q和肿瘤坏死因子相关蛋白（CTRP）超家族的成员。它在脂肪组织中高水平表达，最近作为一种新的脂肪因子出现。在本研究中，我们提供了新的脂肪因子CTRP 3在生殖系统中的生理作用的第一个证据。CTRP 3在成年小鼠睾丸间质间质细胞中特异性表达，睾丸激素在间质间质细胞中产生。CTRP 3以剂量依赖性方式增加TM 3小鼠Leydig细胞的睾酮产生。增加的睾酮产生与类固醇生成蛋白表达的上调有关，例如类固醇生成急性调节（星星）蛋白和胆固醇侧链裂解细胞色素P450（P450 SCC）。此外，在CTRP 3刺激的TM 3 Leydig细胞中，观察到细胞内cAMP（cAMP）浓度和cAMP反应元件结合蛋白（CREB）磷酸化的增加。通过特异性蛋白激酶A（PICA）抑制剂H89抑制该信号通路，阻断了CTRP 3刺激的Leydig细胞中的睾酮产生，表明CTRP 3对睾酮产生的刺激作用与cAMP/PKA信号通路的激活相关。因此，我们的研究结果表明CTRP 3在睾丸类固醇生成中的生理作用，并提供了这种蛋白质激活的细胞内机制的新见解。(C)2012爱思唯尔有限公司保留所有权利。
CTRP3, a paralog of adiponectin, is a member of the C1q and tumor necrosis factor (TNF)-related protein (CTRP) superfamily. It is expressed at high levels in adipose tissue and has recently emerged as a novel adipokine. In the present study, we provide the first evidence for a physiological role of the new adipokine, CTRP3, in the reproductive system. CTRP3 was specifically expressed in interstitial Leydig cells, where testosterone is produced, in the adult mouse testis. CTRP3 increased testosterone production by TM3 mouse Leydig cells in a dose-dependent manner. The increased testosterone production was linked to upregulation of steroidogenic proteins expression, such as steroidogenic acute regulatory (StAR) protein and cholesterol side-chain cleavage cytochrome P450 (P450scc). Moreover, increases in intracellular cyclic AMP (cAMP) concentrations and the phosphorylation of cAMP-response element binding protein (CREB) in CTRP3-stimulated TM3 Leydig cells were observed. Inhibition of this signaling pathway by a specific protein kinase A (PICA) inhibitor, H89, blocked testosterone production in CTRP3-stimulated Leydig cells, suggesting that the stimulatory effect of CTRP3 on testosterone production is associated with activation of the cAMP/PKA signaling pathway. Thus, our results demonstrate a physiological role for CTRP3 in testicular steroidogenesis and provide novel insights in the intracellular mechanisms activated by this protein. (C) 2012 Elsevier Ltd. All rights reserved.