Estrogens and the regulation of glucose metabolism

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.