Abstract
Estrogen can elicit pleiotropic cellular responses via a diversity of estrogen receptors (ERs)—mediated genomic and rapid non-genomic mechanisms. Unlike the genomic responses, where the classical nuclear ERα and ERβ act as transcriptional factors following estrogen binding to regulate gene transcription in estrogen target tissues, the non-genomic cellular responses to estrogen are believed to start at the plasma membrane, leading to rapid activation of second messengers-triggered cytoplasmic signal transduction cascades. The recently acknowledged ER, GPR30 or GPER, was discovered in human breast cancer cells two decades ago and subsequently in many other cells. Since its discovery, it has been claimed that estrogen, ER antagonist fulvestrant, as well as some estrogenic compounds can directly bind to GPER, and therefore initiate the non-genomic cellular responses. Various recently developed genetic tools as well as chemical ligands greatly facilitated research aimed at determining the physiological roles of GPER in different tissues. However, there is still lack of evidence that GPER plays a significant role in mediating endogenous estrogen action in vivo. This review summarizes current knowledge about GPER, including its tissue expression and cellular localization, with emphasis on the research findings elucidating its role in health and disease. Understanding the role of GPER in estrogen signaling will provide opportunities for the development of new therapeutic strategies to strengthen the benefits of estrogen while limiting the potential side effects.
Highlights
Estrogen, 17β-estradiol (E2), is a female sex hormone, which is essential for the development of the female reproductive organs and the secondary sex characteristics [1]
Several studies indicated that G protein-coupled ER (GPER) is activated intracellularly, which diffuses across cell membranes and initiates cellular signaling [31, 84, 85]. These results indicate that GPER is an atypical G protein-coupled receptors (GPCRs), and its intracellular location may dynamically change in response to specific environmental cues and could be tissue-dependent
The results indicated that ovariectomized ERα/β double knockout (DKO) mice were more susceptible to STZ-induced islet apoptosis and diabetes as compared with sham-operated ERα/β DKO mice, but the STZ-induced islet apoptosis and diabetes in ovariectomized ERα/β DKO mice were attenuated by E2 replacement therapy [149], suggesting that E2/GPER signaling is protective against STZ-induced insulin deficient diabetes
Summary
17β-estradiol (E2), is a female sex hormone, which is essential for the development of the female reproductive organs and the secondary sex characteristics [1]. This hormone plays a critical role in the development and function of the male reproductive tract [2]. E2 exerts the comprehensive physiological effects by interacting with estrogen receptors (ERs) and subsequently, activating various signaling cascades that extend from seconds to hours [14, 15]. We provide a brief overview of estrogen signaling and describe the characteristics of its receptors, emphasizing on GPR30, presumably a G protein-coupled ER (GPER). This review summarizes recent research that supports E2-independent effects of GPER in various tissues
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
