Pharmacological Estrogen Administration Causes a FSH-Independent Osteo-Anabolic Effect Requiring ER Alpha in Osteoblasts
| Autor: | Frank Timo Beil, Sebastian Seitz, Tim M. Wintermantel, Michael Amling, Robert P. Marshall, Brenda D. Stride, Johannes Keller, Arndt F. Schilling, Anke Jeschke, Thorsten Schinke, Jan Tuckermann, Günther Schütz |
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| Rok vydání: | 2012 |
| Předmět: |
Anatomy and Physiology
Mouse Osteopenia and Osteoporosis Osteoclasts lcsh:Medicine Estrogen receptor Biochemistry Mice Follicle-stimulating hormone Endocrinology Molecular Cell Biology Membrane Receptor Signaling lcsh:Science Connective Tissue Cells Multidisciplinary Chemistry Animal Models Hormone Receptor Signaling Extracellular Matrix medicine.anatomical_structure Medicine Female Cellular Types hormones hormone substitutes and hormone antagonists Research Article Signal Transduction Protein Binding medicine.medical_specialty Genotype medicine.drug_class Endocrine System Bone Marrow Cells Mice Transgenic Bone resorption Model Organisms Internal medicine medicine Animals Bone Resorption Biology Alleles Crosses Genetic Estrogen receptor beta Osteoblasts Endocrine Physiology lcsh:R Estrogen Receptor alpha Estrogens DNA X-Ray Microtomography Hormones Gene Expression Regulation Estrogen Metabolic Disorders Mutation Women's Health lcsh:Q Cortical bone Follicle Stimulating Hormone Estrogen receptor alpha Hormone |
| Zdroj: | PLoS ONE, Vol 7, Iss 11, p e50301 (2012) PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0050301 |
| Popis: | Postmenopausal osteoporosis is characterized by declining estrogen levels, and estrogen replacement therapy has been proven beneficial for preventing bone loss in affected women. While the physiological functions of estrogen in bone, primarily the inhibition of bone resorption, have been studied extensively, the effects of pharmacological estrogen administration are still poorly characterized. Since elevated levels of follicle-stimulating hormone (FSH) have been suggested to be involved in postmenopausal bone loss, we investigated whether the skeletal response to pharmacological estrogen administration is mediated in a FSH-dependent manner. Therefore, we treated wildtype and FSHβ-deficicent (Fshb(-/-)) mice with estrogen for 4 weeks and subsequently analyzed their skeletal phenotype. Here we observed that estrogen treatment resulted in a significant increase of trabecular and cortical bone mass in both, wildtype and Fshb(-/-) mice. Unexpectedly, this FSH-independent pharmacological effect of estrogen was not caused by influencing bone resorption, but primarily by increasing bone formation. To understand the cellular and molecular nature of this osteo-anabolic effect we next administered estrogen to mouse models carrying cell specific mutant alleles of the estrogen receptor alpha (ERα). Here we found that the response to pharmacological estrogen administration was not affected by ERα inactivation in osteoclasts, while it was blunted in mice lacking the ERα in osteoblasts or in mice carrying a mutant ERα incapable of DNA binding. Taken together, our findings reveal a previously unknown osteo-anabolic effect of pharmacological estrogen administration, which is independent of FSH and requires DNA-binding of ERα in osteoblasts. |
| Databáze: | OpenAIRE |
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