US EPA

2288540 

Journal Article 

MEMBRANE ESTROGEN RECEPTORS - IS IT AN ALTERNATIVE WAY OF ESTROGEN ACTION? 

Soltysik, K; Czekaj, P 

2013 

Yes 

Journal of Physiology and Pharmacology
ISSN: 0867-5910
EISSN: 1899-1505 

64 

2 

129-142 

23756388 

WOS:000320830100001 

The functions of estrogens are relatively well known, however the molecular mechanism of their action is not clear. The classical pathway of estrogen action is dependent on ER alpha and ER beta which act as transcription factors. The effects of this pathway occur within hours or days. In addition, so-called, non-classical mechanism of steroid action dependent on membrane estrogen receptors (mER) was described. In this mechanism the effects of estrogen action are observed in a much shorter time. Here we review the structure and cellular localization of mER, molecular basis of non-classical mER action, physiological role of mER as well as implications of mER action for cancer biology. Finally, some concerns about the new estrogen receptor - GPER and candidates for estrogen receptors - ER-X and ERx, are briefly discussed. It seems that mER is a complex containing signal proteins (signalosome), as IGF receptor, EGF receptor, Ras protein, adaptor protein She, non-receptor kinase c-Src and PI-3K, what rationalizes production of second messengers. Some features of membrane receptors are almost identical if compared to nuclear receptors. Probably, membrane and nuclear estrogen receptors are not separate units, but rather the components of a complex mechanism in which they both cooperate with each other. We conclude that the image of the estrogen receptor as a simple transcription factor is a far-reaching simplification. A better understanding of the mechanisms of estrogen action will help us to design more effective drugs affecting signal pathways depending on both membrane and nuclear receptors. 

membrane estrogen receptor; nuclear estrogen receptor; GPER; ER-X; ERx; signalosome; signal transduction; estrogens