Abstract
Estrogens, predominantly 17β-estradiol (E2), are a class of steroid hormones critical for diverse functions in the body both during normal physiology and disease. Primary actions of E2 include reproduction and development of secondary sexual characteristics. In addition, E2 action is involved in the nervous, immune, vascular, muscular, skeletal, and endocrine systems, all of which contribute to multiple aspects of metabolism. The actions of E2 have traditionally been attributed to the classical nuclear estrogen receptors (ERα and ERβ) that largely mediate transcriptional/genomic activities. However, over the last decade, the G protein-coupled estrogen receptor (GPER/GPR30) has become recognized as a mediator of rapid as well as transcriptional actions of E2, employing both in vitro and in vivo approaches. Recent evidence strongly supports the role of GPER in metabolic regulation. Murine genetic knockout (KO) models and pharmacological tools (agonists and antagonists) represent important approaches to understand the mechanisms of E2 action in physiology and disease via GPER. Studies in cells and GPER KO mice have revealed functions for GPER in the regulation of body weight and metabolism. This chapter focuses on methods relevant for the evaluation of metabolic parameters in vivo, ex vivo, and in vitro. We have emphasized glucose homeostasis through the determination of glucose and insulin tolerance, pancreatic islet function, and glucose uptake. In addition, we describe methods of adipocyte isolation, differentiation of preadipocytes, and evaluation of mitochondrial function.
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Acknowledgments
The authors are supported by grants from the National Institutes of Health (NIH R01 CA163890 and CA194496 to E.R.P.) from Dialysis Clinic, Inc. (E.R.P.), from the University of New Mexico School of Medicine Research Allocation Committee (G.S.) and by the UNM Comprehensive Cancer Center (P30 CA118100), and the Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence (CoBRE, NIH P20 GM121176).
Disclosures: E.R.P. is an inventor on U.S. Patent Nos. 10,251,870, 10,561,648 and 10,682,341 and G.S. and E.R.P. are inventors on U.S. patent No. 10,471,047, all for the therapeutic use of compounds targeting GPER (“Method for treating obesity, diabetes, cardiovascular and kidney diseases by regulating GPR30 /GPER”). E.R.P. is an inventor on U.S. Patent Nos. 7,875,721 and 8,487,100 for GPER-selective ligands and imaging agents (“Compounds for binding to ERα/β and GPR30 , methods of treating disease states and conditions mediated through these receptors and identification thereof”).
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Sharma, G., Prossnitz, E.R. (2022). Assessment of Metabolic Regulation by Estrogen Receptors. In: Eyster, K.M. (eds) Estrogen Receptors. Methods in Molecular Biology, vol 2418. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-1920-9_21
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DOI: https://doi.org/10.1007/978-1-0716-1920-9_21
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