REGULATION OF THE PROGESTERONE-RECEPTOR GENE BY GONADOTROPINS AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE IN RAT GRANULOSA-CELLS
REGULATION OF THE PROGESTERONE-RECEPTOR GENE BY GONADOTROPINS AND CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE IN RAT GRANULOSA-CELLS
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DOI：
10.1210/en.134.2.709
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发表时间：
1994-02-01
期刊：
影响因子：
4.8
通讯作者：
MAYO, KE
中科院分区：
文献类型：
--
作者：
PARKSARGE, OK;MAYO, KE
我们研究了垂体促性腺激素对大鼠卵巢和颗粒细胞孕激素受体(PR)基因表达的影响。促性腺激素(促性腺激素/人绒毛膜促性腺激素)和促性腺激素促性腺激素(FSH)均能在体内快速诱导排卵前卵泡颗粒细胞PRmRNA的表达。促性腺激素也能有效地诱导原代培养的大鼠颗粒细胞PR mRNA的表达，这种作用可以被升高细胞内cAMP的药物(Forsklin或8-bromo-cAMP)所模仿。雌激素不能诱导这些细胞PR基因的表达。CAMP诱导的大鼠颗粒细胞PR mRNA表达可被转录抑制物阻断，但不能被蛋白质合成抑制物阻断。大鼠PR基因5‘侧翼区的结构特征表明，近端的启动子不包含一致的cAMP反应元件。然而，将含有1375碱基的大鼠PR基因片段的荧光素酶融合基因瞬时导入大鼠颗粒细胞后，hCG或Forsklin可使荧光素酶活性增加数倍，而雌激素则不能。这些结果表明，促性腺激素很可能通过cAMP介导的途径发挥作用，能够刺激大鼠颗粒细胞PR基因的转录，并提示了调节孕酮在卵巢内的作用的机制。
We have examined the effects of the pituitary gonadotropins on expression of the progesterone receptor (PR) gene in rat ovary and in granulosa cell cultures. Both gonadotropins (LH/hCG and FSH) rapidly induce PR mRNA expression in the granulosa cells of preovulatory follicles in vivo. Gonadotropins also effectively induce PR mRNA expression in primary cultures of rat granulosa cells, and this action can be mimicked by agents that elevate intracellular cAMP (forskolin or 8-bromo-cAMP). Estrogen does not induce PR mRNA expression in these cells. The cAMP-induced PR mRNA expression in rat granulosa cells is blocked by an inhibitor of transcription, but not by an inhibitor of protein synthesis. Structural characterization of the rat PR gene 5'-flanking region indicates that the proximal promoter does not contain a consensus cAMP response element. However, when luciferase fusion genes containing a 1375-basepair rat PR gene prometer were transiently transfected into rat granulosa cells, luciferase activity could be stimulated several-fold by hCG or forskolin, but not by estrogen. These results indicate that gonadotropins, most likely acting through a pathway mediated by cAMP, are able to stimulate transcription of the PR gene in rat granulosa cells and suggest a mechanism for regulating the intraovarian actions of progesterone.