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Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 15, 2021; 12(10): 1622-1654
Published online Oct 15, 2021. doi: 10.4239/wjd.v12.i10.1622
Estrogens and the regulation of glucose metabolism
Marià Alemany
Marià Alemany, Faculty of Biology, University of Barcelona, Barcelona 08028, Catalonia, Spain
Author contributions: Alemany M is the only author.
Conflict-of-interest statement: The Author declares no conflict of interests for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marià Alemany, PhD, Emeritus Professor, Faculty of Biology, University of Barcelona, Av. Diagonal, 643, Barcelona 08028, Catalonia, Spain. malemany@ub.edu
Received: January 22, 2021
Peer-review started: January 22, 2021
First decision: March 1, 2021
Revised: March 10, 2021
Accepted: April 14, 2021
Article in press: April 14, 2021
Published online: October 15, 2021
Processing time: 263 Days and 17 Hours
Abstract

The main estrogens: estradiol, estrone, and their acyl-esters have been studied essentially related to their classical estrogenic and pharmacologic functions. However, their main effect in the body is probably the sustained control of core energy metabolism. Estrogen nuclear and membrane receptors show an extraordinary flexibility in the modulation of metabolic responses, and largely explain gender and age differences in energy metabolism: part of these mechanisms is already sufficiently known to justify both. With regard to energy, the estrogen molecular species act essentially through four key functions: (1) Facilitation of insulin secretion and control of glucose availability; (2) Modulation of energy partition, favoring the use of lipid as the main energy substrate when more available than carbohydrates; (3) Functional protection through antioxidant mechanisms; and (4) Central effects (largely through neural modulation) on whole body energy management. Analyzing the different actions of estrone, estradiol and their acyl esters, a tentative classification based on structure/effects has been postulated. Either separately or as a group, estrogens provide a comprehensive explanation that not all their quite diverse actions are related solely to specific molecules. As a group, they constitute a powerful synergic action complex. In consequence, estrogens may be considered wardens of energy homeostasis.

Keywords: Estrogens; Insulin; Estrogen receptors; Energy metabolism; Glucose; Antioxidants; Metabolic syndrome

Core Tip: Estrogens play a paramount and continued regulatory role, based on the synergy between the different forms of estrogen to maintain energy (and lipid/glucose) homeostasis. These functions include preventing: oxidative damage, lipid-induced inflammation, excess fat accrual and the complications of excess amino nitrogen. This short incomplete list is fairly close to a recipe for preventing the development of metabolic syndrome; abundant epidemiological and (partial) experimental data help support this assertion. We have to look more widely at estrogens (the different structural-functional types described in the text) to understand their extensive and powerful control of energy homeostasis.