血管活性肠肽（VIP）介导的颗粒细胞中类固醇急性调节蛋白（StAR）的表达和功能。
Vasoactive intestinal peptide (VIP)-mediated expression and function of steroidogenic acute regulatory protein (StAR) in granulosa cells.
机构信息
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, United States.
出版信息
Mol Cell Endocrinol. 2010 Oct 26;328(1-2):93-103. doi: 10.1016/j.mce.2010.07.018. Epub 2010 Jul 23.
Abstract
VIP is a peptide hormone capable of activating the cAMP/PKA pathway and modifying gonadal steroidogenic capacity. Less is known about the molecular mechanisms of VIP-mediated steroidogenesis and its role in regulating the steroidogenic acute regulatory protein (STAR). We examined the impact of VIP on STAR expression and function in immortalized (KK1) and primary mouse granulosa cells, where VIP strongly upregulated STAR expression and steroidogenesis. Inhibitors of the PKA and PKC pathways suggested that both are activated by VIP. VIP did not efficiently phosphorylate STAR (P-STAR); however, VIP together with cAMP-analogs that activate Type II PKA increased P-STAR and further increased steroidogenesis. Our results suggest that VIP-induced STAR expression and function in granulosa cells result from the preferential activation of Type I PKA. Furthermore, the PKA and PKC pathways appear to converge at regulating VIP-mediated Star transcription and translation.
摘要
VIP 是一种能够激活 cAMP/PKA 途径并改变性腺甾体生成能力的肽激素。关于 VIP 介导的甾体生成及其在调节甾体生成急性调节蛋白 (STAR) 中的作用的分子机制知之甚少。我们研究了 VIP 对永生化 (KK1) 和原代小鼠颗粒细胞中 STAR 表达和功能的影响，其中 VIP 强烈地上调 STAR 表达和甾体生成。PKA 和 PKC 途径的抑制剂表明，两者均被 VIP 激活。VIP 不能有效地使 STAR 磷酸化 (P-STAR)；然而，VIP 与激活 II 型 PKA 的 cAMP 类似物一起增加了 P-STAR 并进一步增加了甾体生成。我们的结果表明，VIP 在颗粒细胞中诱导 STAR 的表达和功能是由于 I 型 PKA 的优先激活。此外，PKA 和 PKC 途径似乎在调节 VIP 介导的 Star 转录和翻译方面汇聚。
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