Early Stage Bone Cells Produce Potential Estrogen Substitute

Cells on their way to forming bone also produce an estrogen-like substance that mimics the naturally occurring female sex hormone estradiol, investigators at the Yale School of Medicine reported Monday in the online edition of the Proceedings of the National Academy of Sciences.

Researchers hope such a molecule might provide some of the benefits but, hopefully, not the health risk of traditional hormonal therapies for menopause and bone loss.

Researchers in the laboratories of Thomas L. McCarthy and Michael Centrella in the Department of Surgery isolated this estrogen-like molecule from rat-derived osteoblasts, or cells that can build bones. As the osteoblasts differentiated in culture, they produced a molecule that the investigators tentatively termed “Ob-SERM.” This substance triggered several of the biochemical responses induced by estrogen receptor activation. The osteoblast-derived molecule, however, was in part functionally and chemically distinct from estradiol, raising hopes that it may be a safer alternative to traditional hormone replacement therapies.

Estradiol plays an important role in maintaining skeletal health by balancing the ongoing processes of bone resorption and bone formation that normally occur throughout life. Restoration of estrogen levels after menopause helps to mitigate some of the more harmful side effects of hormone loss that generally occur during aging. However, therapy with native estradiol has also been linked to increased risk of some kinds of cancers.

Other Yale Medical School researchers who contributed to the study include Mary E. Clough and Caren M. Gundberg in the Department of Orthopaedics and Rehabilitation. The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, part of the National Institutes of Health.


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