When women approach menopause, weight gain in fat and low energy spending,” says Deborah Clegg, University of Texas Southwestern Medical Center. Estrogen levels decline and women become increasingly susceptible to obesity and metabolic syndrome.
It acts on the estrogen receptors throughout the body, fat, ovaries and muscles. But when it comes to the influence of hormone metabolism, Clegg suspected receptors in the brain. Others had traced the effects of estrogen on energy balance specifically to estrogen receptor-α (ERa). When his team removed the receptors in the brains of all mice, “mice we are very, very fat,” said Clegg. Animals consumed more calories and burn less.
The researchers showed that mice lacking ERa in a part of the brain (factor-1 hypothalami neurons androgenic or SF1) gain weight without eating more. The loss of ERa in another area of the brain (hypothalamus proopiomelanocortin or POMC neurons) had the opposite effect: the animals eat more without gaining weight. Loss of ERa receptors in the same neurons also led to various problems in ovulation and fertility.
The results suggest that drugs developed to specifically target estrogen receptors in the brain may offer a useful alternative to hormone replacement therapy affect receptors throughout the body. Researchers say they would continue to isolate other effects related to estrogen and symptoms, such as hot flashes and cognition.
“The more we know about the sites of action of estrogen, it is likely that the designer could develop hormone replacement therapies target tissue X, Y or Z,” said Clegg.
