Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University, Innenstadt, Maistrasse, Munich, Germany.
Histochem Cell Biol. 2011 Sep;136(3):289-99. doi: 10.1007/s00418-011-0846-7. Epub 2011 Aug 2.
Estradiol and progesterone mediate their actions by binding to classical nuclear receptors, estrogen receptor α (ERα) and estrogen receptor β (ERβ) and progesterone receptor A and B (PR-A and PR-B) and the non-classical G protein-coupled estrogen receptor (GPER). Several animal knock-out models have shown the importance of the receptors for growth of the oocyte and ovulation. The aim of our study was to identify GPER in human granulosa cells (GC) for the first time. Moreover, the effect of different doses of gonadotropins on estrogen and progesterone receptors in the human ovary should be investigated as follicle stimulating hormone (FSH) and luteinizing hormone (LH) are also responsible for numerous mechanisms in the ovary like induction of the steroid biosynthesis. Human GC were cultured in vitro and stimulated with different doses of recombinant human FSH or LH. Receptor expression was analyzed by immunocytochemistry and quantitative real-time RT-PCR. GPER could be identified for the first time in human GC. It could be shown that high concentrations of LH increase GPER protein expression. Furthermore FSH and LH increased ERβ, PR-A and PR-B significantly on protein level. These findings were verified for high doses of FSH and LH on mRNA level. ERα was not affected with FSH or LH. We assume that gonadotropins induce GPER, ERβ and PR in luteinized granulosa cells.
雌二醇和孕酮通过与经典核受体，即雌激素受体 α（ERα）和雌激素受体 β（ERβ）以及孕激素受体 A 和 B（PR-A 和 PR-B）和非经典 G 蛋白偶联雌激素受体（GPER）结合来发挥作用。几个动物敲除模型表明，受体对于卵母细胞生长和排卵至关重要。我们的研究旨在首次鉴定人颗粒细胞（GC）中的 GPER。此外，还应研究不同剂量的促性腺激素对人卵巢中雌激素和孕激素受体的影响，因为卵泡刺激素（FSH）和黄体生成素（LH）也负责卵巢中的许多机制，如诱导类固醇生物合成。人 GC 在体外培养并接受不同剂量的重组人 FSH 或 LH 刺激。通过免疫细胞化学和实时定量 RT-PCR 分析受体表达。首次在人 GC 中鉴定出 GPER。可以表明，高浓度的 LH 增加了 GPER 蛋白表达。此外，FSH 和 LH 在蛋白质水平上显著增加了 ERβ、PR-A 和 PR-B。这些发现在 FSH 和 LH 的高剂量水平上在 mRNA 水平上得到了验证。FSH 或 LH 对 ERα 没有影响。我们假设促性腺激素诱导黄体化颗粒细胞中的 GPER、ERβ 和 PR。
