title: Estrogen receptor alpha is essential for the proliferation of prostatic smooth muscle cells stimulated by 17β-estradiol and insulin-like growth factor 1.
abstract: Estradiol (E₂) and its receptor estrogen receptor alpha (ERα) are implicated in the pathology of stromal-predominant benign prostatic hyperplasia (BPH). Insulin-like growth factor 1(IGF1) is produced primarily by stromal cells in the prostate. Recent study showed that E₂-mediated regulation of IGF1 in mouse uterus requires the DNA binding ability of ERα. However, the crosstalk between ERα and IGF1 in the prostate has not been addressed yet. Therefore, in this study we employed mouse prostatic smooth muscle cells (PSMCs) as a model to demonstrate that E₂ stimulated the proliferation of PSMCs and up-regulated the expression of IGF1 and its receptor IGF1R as well as cyclin D1 in PSMCs, all of which could be inhibited by shRNA-mediated knockdown of ERα. Furthermore, we found that exogenous IGF1 could not promote cell proliferation and cyclin D1 expression in PSMCs subjected to shRNA-mediated knockdown of ERα. Interestingly, blockage of IGF1R by antibody could inhibit E₂-stimulated PSMCs proliferation. Altogether our present study provides the first line of evidence that there is crosstalk between ERα and IGF1 signaling in PSMCs proliferation in which ERα up-regulates the expression of IGF1 and IGF1R, and IGF1 signaling is indispensable to mediate downstream effects of E₂ and ERα.
authors.affiliation: Research Center of Urology and Andrology, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Zhou
authors.forename: Shiwen
authors.initials: S
authors.lastname: Li
authors.forename: Xinghuan
authors.initials: X
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Cheng
authors.forename: Xiegang
authors.initials: X
authors.lastname: Ding
mesh_terms: D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D011467:Prostate / Q000166:cytology* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D047628:Estrogen Receptor alpha; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1