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OHSU team discovers compound that lacks estrogen's risks

PORTLAND, Ore. A team of Oregon Health & Science University researchers has discovered a compound that offers the benefits of estrogen but lacks the popular hormone replacement therapy's suspected side effects and risks.

Scientists in the OHSU School of Medicine's Department of Physiology and Pharmacology, in collaboration with an organic chemist at the University of California, San Francisco, developed a new selective estrogen receptor modulator (SERM) called STX that shows promise as an alternative to estrogen treatment used by postmenopausal women to relieve symptoms of menopause, such as hot flashes and sleeplessness.

Martin J. Kelly, Ph.D., and Oline K. Rnnekleiv, Ph.D., professors of physiology and pharmacology at OHSU, led the team of investigators that discovered a novel estrogen signaling pathway in nerve cells in the brain. Their findings are published in the Oct. 22 edition of The Journal of Neuroscience.

"The function of STX was really identified from our electrophysiological assay based on testing different (SERM) compounds that acted like estrogen in the central nervous tissue, but not in other tissues susceptible to the cancer-causing effects of estrogens," Kelly said. Other compounds tested included the well-known SERMs tamoxifen and raloxifene, used for the prevention and treatment of breast cancer and osteoporosis, respectively.

STX mimics the effects of estrogen by activating a novel rapid signaling pathway, discovered by Kelly and Rnnekleiv, in nerve cells of the hypothalamus. The hypothalamus is a thumb-sized, central area on the underside of the brain that controls endocrine and autonomic functions, such as ovulation, lactation, stress responses, body temperature and energy balance.

Key to the development of STX was the work of organic chemist Thomas Scanlan, Ph.D., a UCSF professor whose laboratory synthesized the estrogen-like compounds tested in the electrophysiological assays used by Kelly
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Contact: Jonathan Modie
modiej@ohsu.edu
503-494-8231
Oregon Health & Science University
30-Dec-2003


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