The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion.
The Src tyrosine kinase pathway regulates thecal CYP17 expression and androstenedione secretion.
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DOI：
10.1007/s11010-008-9871-9
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发表时间：
2008-11
影响因子：
4.3
通讯作者：
Roby, Katherine F.
中科院分区：
文献类型：
--
作者：
Chaturvedi, Gaurav;Arai, Koji;Terranova, Paul F.;Roby, Katherine F.
为了评估Src酪氨酸激酶在鞘细胞类固醇生成中的作用，我们采用药理学方法，用直接Src激酶抑制剂PP2处理体外富集的小鼠卵巢鞘间质细胞群。用PP2抑制Src增加了基础和福斯克林刺激的雄烯二酮分泌，增加了细胞色素P450 17- α羟化酶（CYP17）启动子活性和稳态mRNA。PP2未改变StAR mRNA的水平。使用PD98059抑制丝裂原活化蛋白激酶激酶（Src活性的下游调节剂）也比单独使用福斯柯林增加了福斯柯林刺激的雄烯二酮分泌，但对雄烯二酮的基础分泌没有影响。Src抑制增加了丝裂原活化的蛋白激酶磷酸酶-1蛋白，降低了SF-1的磷酸化，这与CYP17启动子活性和mRNA水平升高相关。这些结果提示Src酪氨酸激酶参与调节CYP17和鞘雄激素分泌。
In order to evaluate the role of Src tyrosine kinase in thecal cell steroidogenesis, a pharmacological approach was utilized by treating enriched populations of mouse ovarian theca-interstitial cells in vitro with a direct Src kinase inhibitor, PP2. Inhibition of Src with PP2 increased both basal and forskolin-stimulated androstenedione secretion, and increased cytochrome P450 17-alpha hydroxylase-lyase (CYP17) promoter activity and steady state mRNA. PP2 did not change thecal levels of StAR mRNA. Inhibition of mitogen-activated protein kinase kinase, a downstream regulator of Src activity, using PD98059 also increased forskolin-stimulated secretion of androstenedione above forskolin alone, but had no effect on basal secretion of androstenedione. Src inhibition increased mitogen-activated protein kinase phosphatase-1 protein and decreased phosphorylation of SF-1, which correlated with increased CYP17 promoter activity and mRNA levels. These results implicate Src tyrosine kinase in the regulation of CYP17 and thecal androgen secretion.
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