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FSH directly regulates bone mass.

Li Sun·Yuanzhen Peng·Allison C Sharrow·Jameel Iqbal·Zhiyuan Zhang·Dionysios J Papachristou·Samir Zaidi·Ling-Ling Zhu·Beatrice B Yaroslavskiy·Hang Zhou·Alberta Zallone·M Ram Sairam·T Rajendra Kumar·Wei Bo·Jonathan Braun·Luis Cardoso-Landa·Mitchell B Schaffler·Baljit S Moonga·Harry C Blair·Mone Zaidi
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Abstract

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.

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AnimalsBone ResorptionBone and BonesCell DifferentiationCells, CulturedEnzyme ActivationEstrogensExtracellular Signal-Regulated MAP KinasesFemaleFollicle Stimulating HormoneGTP-Binding Protein alpha Subunit, Gi2HumansHypogonadismMiceMice, Inbred C57BLMice, KnockoutNF-kappa BOsteoclastsOsteoporosisProtein SubunitsProto-Oncogene Proteins c-aktReceptors, FSHSignal TransductionJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.

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Li Sun, Yuanzhen Peng, Allison C Sharrow, Jameel Iqbal, Zhiyuan Zhang, Dionysios J Papachristou, Samir Zaidi, Ling-Ling Zhu, Beatrice B Yaroslavskiy, Hang Zhou, Alberta Zallone, M Ram Sairam, T Rajendra Kumar, Wei Bo, Jonathan Braun, Luis Cardoso-Landa, Mitchell B Schaffler, Baljit S Moonga, Harry C Blair, Mone Zaidi. 2006-04-21. FSH directly regulates bone mass.. https://doi.org/10.1016/j.cell.2006.01.051

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