Featured Research

from universities, journals, and other organizations

Getting estrogen's benefits without cancer risk

Date:
June 23, 2010
Source:
UT Southwestern Medical Center
Summary:
Researchers 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.

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 where we can start to think about how to translate these findings to humans."

Women generally have a low risk for heart disease until menopause, when their estrogen levels decline. The hormone has the potential to protect women from heart attack and stroke by maintaining healthy blood vessels, but it also can fuel tumor growth in reproductive tissues. Hormone replacement therapy, which usually includes estrogen, is often used to stave off osteoporosis and symptoms of menopause.

In the study, the researchers examined female mice with high cholesterol and injured carotid arteries, which become substantially blocked if the ovaries have been removed, mimicking diseased arteries in the heart and brain that cause heart attacks and strokes.

When researchers treated the injured mice with the new molecule, the arteries remained clear and unobstructed. Other studies showed that estrogen has the same effect.

"Cholesterol is extremely high in these mice, and the stage is set for them to have severe vascular disease, yet this molecule completely prevents that," Dr. Shaul said.

The team also wanted to determine if the mechanisms that promote blood vessel health are different from those that promote cancer. To do this, they studied how normal and cancerous uterine cells respond to the synthetic molecule. Whereas estrogen caused robust growth of both normal and cancerous uterine cells, the synthetic molecule did not. In addition, in experiments evaluating breast cancer tumor growth in mice, the tumors grew considerably with estrogen but not with the new SERM.

Dr. Shaul said the findings strongly suggest that the molecule helps maintain vascular health without adverse impact on cancer risk. He noted that this approach is likely applicable to both men and women and not limited to older individuals.

Although the molecule used in this study has been tested only in mice, Dr. Shaul and his colleagues are now creating and studying similar molecules for potential use in humans.

Other UT Southwestern researchers participating in the study were Dr. Ken Chambliss, co-lead author and senior research scientist in pediatrics; Dr. Qian Wu, co-lead author and postdoctoral researcher in pediatrics; Dr. Michihisa Umetani, instructor of pediatrics; Dr. Chieko Mineo, assistant professor of pediatrics; Ivan Yuhanna, senior research associate in pediatrics; Drs. Sean Dineen, Sarah Oltmann and Christina Roland, surgery residents; Dr. Rolf Brekken, associate professor of surgery; and Dr. Gail Thomas, former associate professor of internal medicine.

Researchers from the National Institute of Health and Safety; the University of Milan, the University of Illinois at Urbana-Champaign and the University of Cincinnati College of Medicine also contributed to the study.

The study was supported by the National Institute of Health, the American Heart Association, The Lowe Foundation and the Crystal Charity Ball Center for Pediatric Critical Care Research.


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal References:

  1. Ken L. Chambliss, Qian Wu, Sarah Oltmann, Eddy S. Konaniah, Michihisa Umetani, Kenneth S. Korach, Gail D. Thomas, Chieko Mineo, Ivan S. Yuhanna, Sung Hoon Kim, Zeynep Madak-Erdogan, Adriana Maggi, Sean P. Dineen, Christina L. Roland, David Y. Hui, Rolf A. Brekken, John A. Katzenellenbogen, Benita S. Katzenellenbogen and Philip W. Shaul. Non-nuclear estrogen receptor alpha signaling promotes cardiovascular protection but not uterine or breast cancer growth in mice. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI38291
  2. Michael E. Mendelsohn, Richard H. Karas. Rapid progress for non-nuclear estrogen receptor signaling. Journal of Clinical Investigation, 2010; 120 (7): 2277-2279 DOI: 10.1172/JCI43756

Cite This Page:

UT Southwestern Medical Center. "Getting estrogen's benefits without cancer risk." ScienceDaily. ScienceDaily, 23 June 2010. <www.sciencedaily.com/releases/2010/06/100623123353.htm>.
UT Southwestern Medical Center. (2010, June 23). Getting estrogen's benefits without cancer risk. ScienceDaily. Retrieved August 28, 2014 from www.sciencedaily.com/releases/2010/06/100623123353.htm
UT Southwestern Medical Center. "Getting estrogen's benefits without cancer risk." ScienceDaily. www.sciencedaily.com/releases/2010/06/100623123353.htm (accessed August 28, 2014).

Share This




More Health & Medicine News

Thursday, August 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Mini Pacemaker Has No Wires

Mini Pacemaker Has No Wires

Ivanhoe (Aug. 27, 2014) Cardiac experts are testing a new experimental device designed to eliminate major surgery and still keep the heart on track. Video provided by Ivanhoe
Powered by NewsLook.com
After Cancer: Rebuilding Breasts With Fat

After Cancer: Rebuilding Breasts With Fat

Ivanhoe (Aug. 27, 2014) More than 269 million women are diagnosed with breast cancer each year. Many of them will need surgery and radiation, but there’s a new simple way to reconstruct tissue using a patient’s own fat. Video provided by Ivanhoe
Powered by NewsLook.com
Blood Clots in Kids

Blood Clots in Kids

Ivanhoe (Aug. 27, 2014) Every year, up to 200,000 Americans die from a blood clot that travels to their lungs. You’ve heard about clots in adults, but new research shows kids can get them too. Video provided by Ivanhoe
Powered by NewsLook.com
Radio Waves Knock out Knee Pain

Radio Waves Knock out Knee Pain

Ivanhoe (Aug. 27, 2014) Doctors have used radio frequency ablation or RFA to reduce neck and back pain for years. But now, that same technique is providing longer-term relief for patients with severe knee pain. Video provided by Ivanhoe
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins