Researchers At Eli Lilly And Company Provide A New Understanding Of How Estrogen May Impact Women

August 29, 1996

Indianapolis, IN -- Eli Lilly and Company researchers studying the mechanism of action of the investigational compound raloxifene have discovered a new pathway through which estrogen affects various organs, according to an article being published in Science. Their findings may have important physiological implications for women, particularly their skeletal and cardiovascular health.

For several decades, researchers have acknowledged the benefits of estrogen in protecting women from cardiovascular diseases, osteoporosis and, more recently, Alzheimer's disease. However, they have also warned against the potential increase in breast and uterine cancer. And throughout this period, they have searched for an explanation of how estrogen affects various organs of the body so differently.

"The research published in Science gives us a new way of looking at what estrogen is, what estrogen receptors are and how new compounds interact with them to provide potential benefits, such as prevention of osteoporosis and cardiovascular disease, without causing some unfavorable effects, such as possible increases in breast and/or uterine cancer," explained Michael B. Sporn, M.D., professor of pharmacology and medicine at Dartmouth Medical School.

"There are public health implications from this research that we don't even know about yet; cardiovascular diseases, neurodegenerative diseases and various types of cancer all may be affected. This research creates a window of opportunity, showing us that the old model is no longer adequate and providing opportunities to develop new compounds that more effectively target different organs," he added.

In studies conducted with raloxifene, a drug that counters estrogen action in the breast while mimicking it in the bone, the Lilly team, led by molecular biologist Na N. Yang, Ph.D., has discovered a possible explanation for how the same drug may cause different effects, depending on which tissue it is acting in, and how the natural hormone itself manages to adopt so many different guises, according to Science.

"The team has found a second major pathway by which estrogen can regulate body functions," explained John D. Termine, Ph.D., a vice president at Lilly Research Laboratories. "In important nonreproductive tissues, such as the bones, raloxifene communicates with genes in the cell nucleus through a different route than the one traced for estrogens in the breast and other reproductive tissues. This changes the playing field by highlighting the potential of these two different major gene activation pathways." He explained that the clinical impact of this research on the future health of women -- and even men -- could be substantial.

"Beyond showing how estrogen acts in the body, this study is among the first to review multiple pathways that play potential roles in estrogen activity," said Yang. "Perhaps in the future, we may confirm that there is some estrogen for reproduction and other estrogen for bone, the cardiovascular or the central nervous system. It gives us the hope of engineering a drug that will provide the benefits of estrogen without the side effects. This research is just the beginning in a revolutionary approach to health care for the more than 150 million women worldwide with osteoporosis."

Lilly is a global research-based pharmaceutical corporation headquartered in Indianapolis, Indiana, dedicated to creating and delivering superior health care solutions -- by combining pharmaceutical innovation, existing pharmaceutical technology, disease prevention and management and information technologies -- in order to provide customers worldwide with optimal clinical and economic outcomes.
This release contains forward-looking information regarding the potential medical benefits of the investigational compound raloxifene, based on research conducted to date. Clinical studies are ongoing to determine the safety and efficacy of raloxifene. As with any investigational compound, there can be no assurance that preliminary findings will be supported by full-scale clinical trials or that regulatory clearances will be obtained.

Eli Lilly and Company

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