title: G protein-coupled estrogen receptor 1 (GPER 1) mediates estrogen-induced, proliferation of leiomyoma cells.
abstract: 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.
authors.affiliation: a Department of Gynecology , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou City , Zhejiang Province , People's Republic of China .
authors.forename: Xiuxiu
authors.initials: X
authors.lastname: Jiang
authors.affiliation: b Department of Gynecology , The Third Affiliated Hospital of Ningbo University , Ningbo City , Zhejiang Province , People's Republic of China , and.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Ye
authors.affiliation: c Department of Laboratory , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou City , Zhejiang Province , People's Republic of China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Ma
authors.affiliation: c Department of Laboratory , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou City , Zhejiang Province , People's Republic of China.
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.affiliation: a Department of Gynecology , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou City , Zhejiang Province , People's Republic of China .
authors.forename: Ruijin
authors.initials: R
authors.lastname: Wu
authors.affiliation: a Department of Gynecology , Women's Hospital, School of Medicine, Zhejiang University , Hangzhou City , Zhejiang Province , People's Republic of China .
authors.forename: Lin
authors.initials: L
authors.lastname: Jun
mesh_terms: D000328:Adult; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D008875:Middle Aged; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D015854:Up-Regulation; D063186:Uterine Myomectomy; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000601:surgery
chemical_list: D004967:Estrogens; C109584:GPER1 protein, human; D034741:RNA, Small Interfering; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D000077267:Fulvestrant; D004958:Estradiol; D020928:Mitogen-Activated Protein Kinases
keywords: Estrogen; G protein-coupled receptor 30; leiomyoma; mitosis; proliferation