News & Research

By: Almas Eftekhari

Estrogen is a hormone that influences many important functions in the body. In addition to regulating female fertility, estrogen helps maintain normal energy levels, appetite, metabolism, and body weight in both men and women. The hormone serves these functions through a number of distinct receptors, located in different areas of the body, which act locally to elicit a response. Until recently, the sites where estrogen acts to regulate metabolism had yet to be identified.

Association-funded researcher Yong Xu, MD, PhD, from the Baylor College of Medicine, has now uncovered the critical areas in the brain where estrogen acts through specific estrogen receptors, known as ER-α to control metabolism, energy expenditure, and reproduction. Through various experiments with female mice, Dr. Xu and his research team, which also included Association-funded investigator Joel Elmquist, DVM, PhD, from the University of Texas Southwestern Medical Center at Dallas, are the first to narrow down the location of ER-α receptors to two types of neurons in the hypothalamus.

The study results, which were published in Cell Metabolism on October 5, 2011, confirm the mechanism by which estrogen regulates different aspects of female ovulation and fertility, hunger, energy balance, and fat distribution. The researchers observed that female mice lacking ER-α in these hypothalamic neurons developed insatiable appetites, slowed metabolism, and central obesity – a dangerous condition where fat accumulates in and around vital organs in the abdomen, potentially leading to diabetes, heart disease, and stroke.

Women with low levels of estrogen or who are postmenopausal often undergo hormone replacement therapy to avoid obesity and diminishing energy. Unfortunately, this treatment is associated with serious health issues like breast cancer, heart disease, and stroke. Dr. Xu’s research may provide promising targets for treating these women through safer, more selective agents. Furthermore, the study may give insight in selectively combating infertility, obesity, and other diseases that are caused by obesity.

Dr. Xu is currently studying ER-α in male mice brains and suspects to find similar effects.

(Xu Y, Nedungadi TP, Zhu L, Sobhani N, Irani BG, Davis KE, Zhang X, Zou F, Gent LM, Hahner LD, Khan SA, Elias CF, Elmquist JK, Clegg DJ. Distinct Hypothalamic Neurons Mediate Estrogenic Effects on Energy Homeostasis and Reproduction. Cell Metabolism. 5 Oct 2011; 14 (4): 453-465 DOI: 10.1016/j.cmet.2011.08.009)