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10.1016/j.jsbmb.2015.06.014

http://scihub22266oqcxt.onion/10.1016/j.jsbmb.2015.06.014
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suck abstract from ncbi


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pmid26189910      J+Steroid+Biochem+Mol+Biol 2015 ; 153 (ä): 114-26
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  • What have we learned about GPER function in physiology and disease from knockout mice? #MMPMID26189910
  • Prossnitz ER; Hathaway HJ
  • J Steroid Biochem Mol Biol 2015[Sep]; 153 (ä): 114-26 PMID26189910show ga
  • Estrogens, predominantly 17?-estradiol, exert diverse effects throughout the body in both normal and patho-physiology, during development and in reproductive, metabolic, endocrine, cardiovascular, nervous, musculoskeletal and immune systems. Estrogen and its receptors also play important roles in carcinogenesis and therapy, particularly for breast cancer. In addition to the classical nuclear estrogen receptors (ER? and ER?) that traditionally mediate predominantly genomic signaling, the G protein-coupled estrogen receptor GPER has become recognized as a critical mediator of rapid signaling in response to estrogen. Mouse models, and in particular knockout (KO) mice, represent an important approach to understand the functions of receptors in normal physiology and disease. Whereas ER? KO mice display multiple significant defects in reproduction and mammary gland development, ER? KO phenotypes are more limited, and GPER KO exhibit no reproductive deficits. However, the study of GPER KO mice over the last six years has revealed that GPER deficiency results in multiple physiological alterations including obesity, cardiovascular dysfunction, insulin resistance and glucose intolerance. In addition, the lack of estrogen-mediated effects in numerous tissues of GPER KO mice, studied in vivo or ex vivo, including those of the cardiovascular, endocrine, nervous and immune systems, reveals GPER as a genuine mediator of estrogen action. Importantly, GPER KO mice have also revealed roles for GPER in breast carcinogenesis and metastasis. In combination with the supporting effects of GPER-selective ligands and GPER knockdown approaches, GPER KO mice demonstrate the therapeutic potential of targeting GPER activity in diseases as diverse as obesity, diabetes, multiple sclerosis, hypertension, atherosclerosis, myocardial infarction, stroke and cancer.
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