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

  • Geetanjali Sharma
  • Eric R. Prossnitz
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1043)


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.


Estrogen GPER Metabolism Inflammation Insulin resistance Obesity 



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.


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© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Division of Molecular Medicine, Department of Internal MedicineUniversity of New Mexico Health Sciences CenterAlbuquerqueUSA
  2. 2.Division of Molecular Medicine, Department of Internal Medicine, and Autophagy, Inflammation and Metabolism Center of Biomedical Research ExcellenceUniversity of New Mexico Health Sciences CenterAlbuquerqueUSA
  3. 3.University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences CenterAlbuquerqueUSA

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