Progress in the molecular understanding of central regulation of body weight by estrogens

OBJECTIVE Estrogens can act in the brain to prevent body weight gain. Tremendous research efforts have been focused on estrogen physiology in the brain in the context of body weight control; estrogen receptors and the related signals have been attractive targets for development of new obesity therapies. The objective is to review recent findings on these aspects. METHODS Recent studies that used conventional and conditional knockout mouse strains to delineate the cellular and molecular mechanisms for the beneficial effects of estrogens on body weight balance are reviewed. Emerging genetic tools that could further benefit the field of estrogen research and a newly developed estrogen-based regimen that produces body weight-lowering benefits also are discussed. RESULTS The body weight-lowering effects of estrogens are mediated by multiple forms of estrogen receptors in different brain regions through distinct but coordinated mechanisms. Both rapid signals and "classic" nuclear receptor actions of estrogen receptors appear to contribute to estrogenic regulation of body weight. CONCLUSIONS Estrogen receptors and associated signal networks are potential targets for obesity treatment, and further investigations are warranted.