Bone turnover across the menopause transition : The role of gonadal inhibins.
Accumulating evidence demonstrates increasing bone turnover and bone loss in women prior to menopause and decreases in serum estradiol levels. Increased follicle-stimulating hormone levels have been correlated with some of these peri-menopausal changes. However, decreases in gonadal inhibins of the transforming growth factor (TGF)-beta superfamily strongly correlate with increases in bone formation and resorption markers across the menopause transition and predict lumbar bone mass in peri-menopausal women, likely as a result of direct inhibin suppression of osteoblastogenesis and osteoclastogenesis. Inhibins bind specifically to cells during osteoblastogenesis and osteoclastogenesis. They can block bone morphogenetic protein (BMP)-stimulated osteoblast and osteoclast development as well as BMP-stimulated SMAD1 phosphorylation, likely via inhibin-beta-glycan sequestration of BMP Type II receptor (BMPRII). Interestingly, continuous in vivo exposure to inhibin A is anabolic and protective against gonadectomy-induced bone loss in mice, suggesting that inhibins contribute to the endocrine regulation of bone metabolism via a bimodal mechanism of action whereby cycling inhibin exposure suppresses bone turnover and continuous exposure to inhibins is anabolic.
Nicks
Kristy M
KM
Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Fowler
Tristan W
TW
Akel
Nisreen S
NS
Perrien
Daniel S
DS
Suva
Larry J
LJ
Gaddy
Dana
D
D000818:Animals; D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D007265:Inhibins / Q000494:pharmacology / Q000502:physiology; D008593:Menopause / Q000097:blood / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology
D015415:Biomarkers; D007265:Inhibins
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