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Researchers find key to getting estrogen's benefits without cancer risk
Date:6/23/2010

DALLAS June 23, 2010 Researchers at UT Southwestern Medical Center have pinpointed a set of biological mechanisms through which estrogen confers its beneficial effects on the cardiovascular system, independent of the hormone's actions on cancer. Their investigation suggests that drugs targeting a specific subpopulation of estrogen receptors found outside the cell nucleus might activate the cardiovascular benefits of estrogen without increasing cancer risk.

"Finding a way to get the beneficial effects of estrogen without increasing a woman's risk of cancer is something that could make a big difference to a lot of people," said Dr. Philip Shaul, professor of pediatrics.

Dr. Shaul and UT Southwestern colleagues created and tested in mice a synthetic molecule to determine the mechanisms by which estrogen promotes blood vessel health. Their findings are available online and in the July 1 issue of the Journal of Clinical Investigation.

Estrogen receptors or molecular "docking points" for the hormone usually are found in the cell nucleus. A small subpopulation is also found outside the nucleus of certain cells, including the endothelial cells that line arteries and veins.

Dr. Shaul, the study's senior author, said the new molecule is a unique selective estrogen recaptor modulator (SERM). Tamoxifen, a drug taken by millions of breast cancer patients, is also a SERM.

"We have discovered that the small population of estrogen receptors outside the nucleus of endothelial cells has a unique means to activate cell growth and migration, which are important to blood vessel maintenance and repair, and to regulate the production of nitric oxide, which is a protective molecule in the vascular system," he said. "Whereas all existing estrogen-related drugs change the function of the nuclear receptors which stimulate cancer cell growth, the synthetic molecule targets only the non-nuclear estrogen receptors. We're at the stage
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Contact: Kristen Holland Shear
kristen.hollandshear@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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