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Ann Arbor, MI, USA. Women with depression may be much more likely than men to get relief from a commonly used, inexpensive antidepressant drug, a new national study finds.
But many members of both se...
Urbana, IL, USA. The main estrogen in the female body is estradiol. Doctors often prescribe Hormone Replacement (HT) regimens that only mimic the effects of estradiol, such as conjugated estrogens an...
St. Louis, MO, USA. The triumvirate of sex hormones — estrogen, progesterone, and testosterone — have cycles of rise and fall in our bloodstreams that influence and respond to other changes...
New Haven, CT, USA. The naturally occurring female sex hormone 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.
Restoring estrogen levels after menopause helps to mitigate some of the more harmful side effects of hormone loss that generally occur during aging.
Researchers have now discovered that cells on their way to forming bone also produce an estrogen-like substance that mimics estradiol. 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.
Expression of an estrogen receptor agonist in differentiating osteoblast cultures. Thomas L. McCarthy, Mary E. Clough, Caren M. Gundberg, and Michael Centrella. PNAS 2008 105(19):7022-7; 10.1073 / pnas.0800085105.
Researchers 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.
In addition to Thomas L. McCarthy and Michael Centrella , 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.
Expression of an estrogen receptor agonist in differentiating osteoblast cultures. Thomas L. McCarthy, Mary E. Clough, Caren M. Gundberg, and Michael Centrella. PNAS 2008 105(19):7022-7; 10.1073 / pnas.0800085105.
Abstract. Osteoblasts respond in direct and indirect ways to estrogens, and age-dependent changes in hormone levels and bone health can be limited by focused hormone replacement therapy. In this study, we report the release and isolation of an estrogen receptor agonist from osteoblast cultures. This entity reprises many aspects of estradiol activity in isolated osteoblasts, but differs from authentic estradiol by several biochemical and physical criteria. At levels that occur in conditioned medium from differentiating osteoblast cultures, the agonist directly drives gene expression through estrogen-sensitive response elements, activates the obligate osteoblast transcription factor Runx2, and potently enhances Smad-dependent gene expression in response to TGF-β, but exhibits relatively lesser suppressive effects on gene expression through C/EBP and AP-1-binding protein transcription factors. Estrogen receptor agonist activity is resistant to heating at 100°C and separable from the bulk of the remaining alcohol- and hexane-soluble molecules by C18 chromatography. MS and molecular fragmentation analyses predict a Mr of 415.2 to 437.2. Therefore, in addition to earlier studies showing that osteoblasts readily respond to and metabolize various sex steroid-like substrates, we find that they also generate a potent estrogen receptor agonist during differentiation in vitro. Changes in the availability of a molecule like this within bone may relate to differences in skeletal integrity with aging or metabolic disease.
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Researchers isolated this estrogen-like molecule from rat-derived osteoblasts, or cells that can build bones.
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