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Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity pp 427–453Cite as

G-Protein-Coupled Estrogen Receptor (GPER) and Sex-Specific Metabolic Homeostasis

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1043))

Abstract

Obesity and metabolic syndrome display disparate prevalence and regulation between males and females. Human, as well as rodent, females with regular menstrual/estrous cycles exhibit protection from weight gain and associated chronic diseases. These beneficial effects are predominantly attributed to the female hormone estrogen, specifically 17β-estradiol (E2). E2 exerts its actions via multiple receptors, nuclear and extranuclear estrogen receptor (ER) α and ERβ, and the G-protein-coupled estrogen receptor (GPER, previously termed GPR30). The roles of GPER in metabolic homeostasis are beginning to emerge but are complex and remain unclear. The discovery of GPER-selective pharmacological agents (agonists and antagonists) and the availability of GPER knockout mice have significantly enhanced our understanding of the functions of GPER in normal physiology and disease. GPER action manifests pleiotropic effects in metabolically active tissues such as the pancreas, adipose, liver, and skeletal muscle. Cellular and animal studies have established that GPER is involved in the regulation of body weight, feeding behavior, inflammation, as well as glucose and lipid homeostasis. GPER deficiency leads to increased adiposity, insulin resistance, and metabolic dysfunction in mice. In contrast, pharmacologic stimulation of GPER in vivo limits weight gain and improves metabolic output, revealing a promising novel therapeutic potential for the treatment of obesity and diabetes.

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Acknowledgments

The authors were supported by research grants from the National Institutes of Health (NIH R01 CA127731, CA163890, and CA194496 to ERP), Dialysis Clinic, Inc. (to ERP), and by the UNM Comprehensive Cancer Center (P30 CA118100).

Competing Interests

GS and ERP are inventors on a US patent application for the therapeutic use of compounds targeting GPER. ERP is an inventor on US patent Nos. 7,875,721 and 8,487,100 for GPER-selective ligands and imaging agents.

Author information

Authors and Affiliations

  1. Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Geetanjali Sharma

  2. Division of Molecular Medicine, Department of Internal Medicine, and Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Eric R. Prossnitz

  3. University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM, USA

    Eric R. Prossnitz

Authors
  1. Geetanjali Sharma
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  2. Eric R. Prossnitz
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Correspondence to Geetanjali Sharma or Eric R. Prossnitz .

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Editors and Affiliations

  1. Department of Medicine, Section of Endocrinology and Metabolism, Tulane University Health Sciences Center, School of Medicine, New Orleans, Louisiana, USA

    Franck Mauvais-Jarvis

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Sharma, G., Prossnitz, E.R. (2017). G-Protein-Coupled Estrogen Receptor (GPER) and Sex-Specific Metabolic Homeostasis. In: Mauvais-Jarvis, F. (eds) Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity. Advances in Experimental Medicine and Biology, vol 1043. Springer, Cham. https://doi.org/10.1007/978-3-319-70178-3_20

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