Choosing the right message. synthetic hormones that bypass the traditional route of estrogen (left) and activate the "nongenotropic" track (right) could prevent bone loss without side effects.
despite concerns about the risks of hormone replacement therapy for menopausal women, a benefit is clear: It makes bones stronger. Now a study suggests that it might be possible to maintain the benefits of estrogen while minimizing its risks. A synthetic hormone has been shown to stimulate bone strength in mice without affecting the reproductive organs.
estrogen makes women less likely to develop osteoporosis and suffer debilitating fractures. But this deal comes with an increased risk of breast cancer, pulmonary embolism, myocardial infarction and stroke ( Science , 19 July, p. 325). Rationale The effects of this estrogen on various tissues can count on various cell signaling cascades, a team led by Stavros Manolagas the University of Arkansas for Medical Sciences in Little Rock identified a synthetic hormone called estren that activates a sub all these pathways.
Estren Tinkers with cell building teams that continuously reshape the bone. At one point, Manolagas said, there are 5 million to 10 million sites on a human skeleton which cells called osteoclasts dig trenches in the tiny bones that are filled by bone forming osteoblasts. After menopause, osteoclasts ahead osteoblasts, which makes them more porous and brittle bone.
Manolagas team found that in the test tube, both estrogen and estren encouraged osteoclasts to self-destruction while extending the lifespan of osteoblasts. And in mice whose ovaries were removed, both compounds increased bone density and strength. But they had markedly different effects on the reproductive organs, the team reports in the October issue 25 Science . In mice ovariectomized, uterus loses almost two-thirds of its weight. Estrogen, but not estren, prevents this loss. And while estrogen stimulates the growth of breast cancer cells in culture, estrene not. The reason Manolagas said, is that estren an active way "nongenotropic" signaling that affects the bones but not the reproductive organs.
What compounds such as estren will be useful in humans remains to be seen. "If compounds such as estrogen could be used to maintain bone density with little or no side effects in older women, it would be huge," says molecular endocrinologist Geoffrey Greene of the University of Chicago.
Related Sites
Manolagas the site of
Greene site
basic information about osteoporosis of the National Institute on aging
information and resources on HRT NIH
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