El-Hefnawy T, Zeleznik A J
Department of Physiology and Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Endocrinology. 2001 Oct;142(10):4357-62. doi: 10.1210/endo.142.10.8438.
Follicular development is associated with both proliferation and differentiation of granulosa cells under the control of FSH. We show that regulation of genes involved in cellular proliferation by FSH can be functionally separated from the regulation of genes involved in granulosa cell differentiation by synergistic actions of activin and T. Incubation of undifferentiated rat granulosa cells with FSH, forskolin, activin-A, or T alone did not influence either the expression of the proliferation-associated genes cyclin D2 and proliferating cell nuclear antigen or the differentiation-associated genes P450 aromatase, LH receptor, P450 cholesterol side-chain cleavage enzyme, and 3 beta-hydroxysteroid dehydrogenase. However, when granulosa cells were stimulated with either FSH or forskolin in the presence of activin-A, significant increases (P < 0.05) were observed for cyclin D2 and proliferating cell nuclear antigen at both the mRNA and protein levels as well as mRNAs for P450 aromatase, LH receptor, P450 cholesterol side-chain cleavage enzyme and 3 beta-hydroxysteroid dehydrogenase. Although T synergized with FSH to increase the expression of mRNAs for P450 aromatase, LH receptor, P450 cholesterol side-chain cleavage enzyme, and 3 beta-hydroxysteroid dehydrogenase, it did not interact with FSH to increase the expression of mRNAs for cyclin D2 and proliferating cell nuclear antigen. The differences in the actions of activin and T could provide a cellular mechanism by which FSH-regulated granulosa cell proliferation could be functionally separated from FSH-regulated granulosa cell differentiation.
在促卵泡激素（FSH）的控制下，卵泡发育与颗粒细胞的增殖和分化相关。我们发现，FSH对参与细胞增殖的基因的调控在功能上可与激活素和睾酮（T）的协同作用对参与颗粒细胞分化的基因的调控区分开来。将未分化的大鼠颗粒细胞单独与FSH、福斯可林、激活素A或睾酮孵育，对增殖相关基因细胞周期蛋白D2和增殖细胞核抗原的表达以及分化相关基因细胞色素P450芳香化酶、促黄体生成素（LH）受体、细胞色素P450胆固醇侧链裂解酶和3β-羟基类固醇脱氢酶均无影响。然而，当颗粒细胞在激活素A存在的情况下用FSH或福斯可林刺激时，细胞周期蛋白D2和增殖细胞核抗原在mRNA和蛋白质水平以及细胞色素P450芳香化酶、LH受体、细胞色素P450胆固醇侧链裂解酶和3β-羟基类固醇脱氢酶的mRNA均显著增加（P<0.05）。虽然睾酮与FSH协同增加细胞色素P450芳香化酶、LH受体、细胞色素P450胆固醇侧链裂解酶和3β-羟基类固醇脱氢酶的mRNA表达，但它不与FSH相互作用增加细胞周期蛋白D2和增殖细胞核抗原的mRNA表达。激活素和睾酮作用的差异可能提供一种细胞机制，通过该机制FSH调节的颗粒细胞增殖在功能上可与FSH调节的颗粒细胞分化区分开来。
