跳转至内容
Merck
  • Opposite effects of tamoxifen on metabolic syndrome-induced bladder and prostate alterations: a role for GPR30/GPER?

Opposite effects of tamoxifen on metabolic syndrome-induced bladder and prostate alterations: a role for GPR30/GPER?

The Prostate (2013-09-17)
P Comeglio, A Morelli, I Cellai, L Vignozzi, E Sarchielli, S Filippi, E Maneschi, F Corcetto, C Corno, M Gacci, G B Vannelli, M Maggi
摘要

BPH and LUTS have been associated to obesity, hypogonadism, and metabolic syndrome (MetS). MetS-induced prostate and bladder alterations, including inflammation and tissue remodeling, have been related to a low-testosterone and high-estrogen milieu. In addition to ERs, GPR30/GPER is able to mediate several estrogenic non-genomic actions. Supplementing a subgroup of MetS rabbits with tamoxifen, we analyzed the in vivo effects on MetS-induced prostate and bladder alterations. The effects of selective ER/GPER ligands and GPER silencing on prostate inflammation were also studied in vitro using hBPH cells. ERα, ERβ, and PR expression was upregulated in MetS bladder, where tamoxifen decreased ERα and PR expression, further stimulating ERβ. In addition, tamoxifen-dosing decreased MetS-induced overexpression of inflammatory and tissue remodeling genes. In prostate, sex steroid receptors, pro-inflammatory and pro-fibrotic genes were upregulated in MetS. However, tamoxifen did not affect them and even increased COX-2. In hBPH cells, 17β-estradiol increased IL-8 secretion, an effect blunted by co-treatment with GPER antagonist G15 but not by ER antagonist ICI 182,780, which further increased it. GPER agonist G1 dose-dependently (IC50  = 1.6 nM) induced IL-8 secretion. In vitro analysis demonstrated that GPER silencing reverted these stimulatory effects. GPER can be considered the main mediator of estrogen action in prostate, whereas in bladder the mechanism appears to rely on ERα, as indicated by in vivo experiments with tamoxifen dosing. Limiting the effects of the MetS-induced estrogen action via GPER could offer new perspectives in the management of BPH/LUTS, whereas tamoxifen dosing showed potential benefits in bladder.

材料
货号
品牌
产品描述

Sigma-Aldrich
单克隆抗-肌动蛋白,α-平滑肌, clone 1A4, ascites fluid
货号
包装规格
是否有货
价格
数量
Sigma-Aldrich
抗-山羊IgG(全分子)–FITC 兔抗, affinity isolated antibody, buffered aqueous solution
货号
包装规格
是否有货
价格
数量
Sigma-Aldrich
Rabbit Anti-Goat IgG, H & L Chain Specific Peroxidase Conjugate, liquid, Calbiochem®
货号
包装规格
是否有货
价格
数量