G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced, proliferation of leiomyoma cells.
G protein-coupled estrogen receptor 1 (GPER-1, formerly known as GPR30) has been proposed as the receptor for estrogen-induced, growth of leiomyomas though its precise mechanisms of action are not clear. We obtained leiomyoma cells (LC) and normal smooth muscle cells from 28 women (n = 28, median age 38 years, median parity 1.0). We incubated them with 17-β estradiol (E(2)), after blocking, or upregulating, expression of GPER-1 with ICI182,780 (a GPER-1 agonist) and siGPR30, respectively. We evaluated the role of GPER-1 in the mitogen-activated protein kinase (MAPK) signaling pathway using Western blot analysis. We studied cell proliferation with 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide, and, mitotic activity with phosphohistone H3 (PPH3) expression in leiomyoma, and, matched, normal, smooth muscle tissues using standard immunohistochemistry. Downregulation of GPER-1 expression with siGPR30 partially attenuated the E(2)-activated MAPK signaling pathway (p < 0.01). Upregulation of GPER-1 with ICI182,780 enhanced the E(2)-activated MAPK signaling pathway (p < 0.01). ICI182,780 enhanced E(2)-induced proliferation of LC (p < 0.01), while knock down of the GPER-1 gene with GPER-1 small interfering RNA partially inhibited E(2)-induced cell proliferation (p < 0.01). There were no significant differences in PPH3 expression between LCs and normal smooth muscle tissues (p > 0.05). Neither ICI182,780 nor siGPR30 increased mitosis in LCs (p > 0.05). Our results indicate that GPER-1 mediates proliferation of estrogen-induced, LC by activating the MAPK pathway, and, not by promoting mitosis.
['Jiang|Xiuxiu|X|', 'Ye|Xiaolei|X|', 'Ma|Junyan|J|', 'Li|Wen|W|', 'Wu|Ruijin|R|', 'Jun|Lin|L|']
D000328:Adult D015153:Blotting, Western D049109:Cell Proliferation D002478:Cells, Cultured D015536:Down-Regulation D004958:Estradiol D004967:Estrogens D005260:Female D000077267:Fulvestrant D006801:Humans D007150:Immunohistochemistry D007889:Leiomyoma D008875:Middle Aged D020928:Mitogen-Activated Protein Kinases D008938:Mitosis D032389:Myocytes, Smooth Muscle D034741:RNA, Small Interfering D011960:Receptors, Estrogen D043562:Receptors, G-Protein-Coupled D015398:Signal Transduction D015854:Up-Regulation D063186:Uterine Myomectomy D014594:Uterine Neoplasms
Estrogen proliferation leiomyoma mitosis G protein-coupled receptor 30