FSH Directly Regulates Bone Mass
Copyright policy )FSH Directly Regulates Bone Mass
Postmenopausal osteoporosis, a global public health problem, has for decades been attributed solely to declining estrogen levels. Although FSH levels rise sharply in parallel, a direct effect of FSH on the skeleton has never been explored. We show that FSH is required for hypogonadal bone loss. Neither FSHbeta nor FSH receptor (FSHR) null mice have bone loss despite severe hypogonadism. Bone mass is increased and osteoclastic resorption is decreased in haploinsufficient FSHbeta+/- mice with normal ovarian function, suggesting that the skeletal action of FSH is estrogen independent. Osteoclasts and their precursors possess G(i2alpha)-coupled FSHRs that activate MEK/Erk, NF-kappaB, and Akt to result in enhanced osteoclast formation and function. We suggest that high circulating FSH causes hypogonadal bone loss.
- University of Pittsburgh United States
- University of California, San Francisco United States
- University of Pittsburgh at Bradford United States
- Montreal Clinical Research Institute Canada
- University of California, Los Angeles United States
Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Hypogonadism, NF-kappa B, Osteoclasts, Cell Differentiation, Estrogens, Bone and Bones, Enzyme Activation, Mice, Inbred C57BL, Mice, Protein Subunits, Animals, Humans, Osteoporosis, Female, Bone Resorption, Follicle Stimulating Hormone, GTP-Binding Protein alpha Subunit, Gi2, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured
Mice, Knockout, Biochemistry, Genetics and Molecular Biology(all), Hypogonadism, NF-kappa B, Osteoclasts, Cell Differentiation, Estrogens, Bone and Bones, Enzyme Activation, Mice, Inbred C57BL, Mice, Protein Subunits, Animals, Humans, Osteoporosis, Female, Bone Resorption, Follicle Stimulating Hormone, GTP-Binding Protein alpha Subunit, Gi2, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured
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