title: Reduced prostate branching morphogenesis in stromal fibroblast, but not in epithelial, estrogen receptor α knockout mice.
abstract: Early studies suggested that estrogen receptor alpha (ERα) is involved in estrogen-mediated imprinting effects in prostate development. We recently reported a more complete ERα knockout (KO) mouse model via mating β-actin Cre transgenic mice with floxed ERα mice. These ACTB-ERαKO male mice showed defects in prostatic branching morphogenesis, which demonstrates that ERα is necessary to maintain proliferative events in the prostate. However, within which prostate cell type ERα exerts those important functions remains to be elucidated. To address this, we have bred floxed ERα mice with either fibroblast-specific protein (FSP)-Cre or probasin-Cre transgenic mice to generate a mouse model that has deleted ERα gene in either stromal fibroblast (FSP-ERαKO) or epithelial (pes-ERαKO) prostate cells. We found that circulating testosterone and fertility were not altered in FSP-ERαKO and pes-ERαKO male mice. Prostates of FSP-ERαKO mice have less branching morphogenesis compared to that of wild-type littermates. Further analyses indicated that loss of stromal ERα leads to increased stromal apoptosis, reduced expression of insulin-like growth factor-1 (IGF-1) and FGF10, and increased expression of BMP4. Collectively, we have established the first in vivo prostate stromal and epithelial selective ERαKO mouse models and the results from these mice indicated that stromal fibroblast ERα plays important roles in prostatic branching morphogenesis via a paracrine fashion. Selective deletion of the ERα gene in mouse prostate epithelial cells by probasin-Cre does not affect the regular prostate development and homeostasis.
authors.affiliation: Departments of Urology and Pathology, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Chiuan-Ren
authors.initials: CR
authors.lastname: Yeh
authors.forename: Chih-Rong
authors.initials: CR
authors.lastname: Shyr
authors.forename: Hsiu-Hsia
authors.initials: HH
authors.lastname: Lin
authors.forename: Jun
authors.initials: J
authors.lastname: Da
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D055415:Bone Morphogenetic Protein 4 / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D005298:Fertility; D051526:Fibroblast Growth Factor 10 / Q000235:genetics / Q000378:metabolism; D051523:Fibroblast Growth Factor 7 / Q000235:genetics / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D005838:Genotype; D018398:Homeodomain Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D029584:Prostatic Secretory Proteins / Q000378:metabolism; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D013076:Sperm Count; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C525810:Bmp4 protein, mouse; D055415:Bone Morphogenetic Protein 4; D047628:Estrogen Receptor alpha; C496464:Fgf10 protein, mouse; C496454:Fgf7 protein, mouse; D051526:Fibroblast Growth Factor 10; D018398:Homeodomain Proteins; C102837:Nkx3-1 protein, mouse; D029584:Prostatic Secretory Proteins; D011944:Receptors, Androgen; D014157:Transcription Factors; C043076:beta-microseminoprotein; C519530:insulin-like growth factor-1, mouse; D051523:Fibroblast Growth Factor 7; D013739:Testosterone; D007334:Insulin-Like Growth Factor I