A critical review of fundamental controversies in the field of GPR30 research

被引:134
作者
Langer, Gernot [5 ]
Bader, Benjamin [5 ]
Meoli, Luca [4 ]
Isensee, Joerg [3 ,4 ]
Delbeck, Martina [2 ]
Noppinger, Patricia Ruiz [4 ]
Otto, Christiane [1 ]
机构
[1] Bayer Schering Pharma AG, TRG Womens Healthcare, D-13342 Berlin, Germany
[2] Bayer Schering Pharma AG, Cardiol Res, D-42096 Wuppertal, Germany
[3] Max Planck Inst Mol Genet, Dept Human Mol Genet, D-14195 Berlin, Germany
[4] Charite, Cardiovasc Res Ctr, D-10115 Berlin, Germany
[5] Bayer Schering Pharma AG, Screening Berlin, Lead Generat & Optimizat, D-13342 Berlin, Germany
关键词
GPR30; GPR30-deficient mice; PROTEIN-COUPLED RECEPTOR-30; ESTROGEN-RECEPTOR; GENE-EXPRESSION; ER-ALPHA; ACTIVATION; TAMOXIFEN; CLONING; GROWTH; G-PROTEIN-COUPLED-RECEPTOR-30; INHIBITION;
D O I
10.1016/j.steroids.2009.12.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The female sex hormone estradiol plays an important role in reproduction, mammary gland development, bone turnover, metabolism, and cardiovascular function. The effects of estradiol are mediated by two classical nuclear receptors, estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta). In 2005, G-protein-coupled receptor 30 (GPR30) was claimed to act as a non-classical estrogen receptor that was also activated by the ER alpha and ER beta antagonists tamoxifen and fulvestrant (ICI 182780). Despite many conflicting results regarding the potential role of GPR30 as an estrogen receptor, the official nomenclature was changed to GPER (G-protein-coupled estrogen receptor). This review revisits the inconsistencies that still exist in the literature and focuses on selected publications that basically address the following two questions: what is the evidence for and against the hypothesis that GPR30 acts as an estrogen receptor? What is the potential in vivo role of GPR30? Thus, in the first part we focus on conflicting results from in vitro studies analysing the subcellular localization of GPR30, its ability to bind (or not to bind) estradiol and to signal (or not to signal) in response to estradiol. In the second part, we discuss the strengths and limitations of four available GPR30 mouse models. We elucidate the potential impact of different targeting strategies on phenotypic diversity. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:603 / 610
页数:8
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