title: FSH directly regulates bone mass.
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.
authors.affiliation: Mount Sinai Bone Program, Department of Medicine and Department of Orthopedics, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Peng
authors.forename: Allison C
authors.initials: AC
authors.lastname: Sharrow
authors.forename: Jameel
authors.initials: J
authors.lastname: Iqbal
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.forename: Dionysios J
authors.initials: DJ
authors.lastname: Papachristou
authors.forename: Samir
authors.initials: S
authors.lastname: Zaidi
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhu
authors.forename: Beatrice B
authors.initials: BB
authors.lastname: Yaroslavskiy
authors.forename: Hang
authors.initials: H
authors.lastname: Zhou
authors.forename: Alberta
authors.initials: A
authors.lastname: Zallone
authors.forename: M Ram
authors.initials: MR
authors.lastname: Sairam
authors.forename: T Rajendra
authors.initials: TR
authors.lastname: Kumar
authors.forename: Wei
authors.initials: W
authors.lastname: Bo
authors.forename: Jonathan
authors.initials: J
authors.lastname: Braun
authors.forename: Luis
authors.initials: L
authors.lastname: Cardoso-Landa
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Schaffler
authors.forename: Baljit S
authors.initials: BS
authors.lastname: Moonga
authors.forename: Harry C
authors.initials: HC
authors.lastname: Blair
authors.forename: Mone
authors.initials: M
authors.lastname: Zaidi
mesh_terms: D000818:Animals; D001862:Bone Resorption; D001842:Bone and Bones / Q000033:anatomy & histology / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004789:Enzyme Activation; D004967:Estrogens / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005640:Follicle Stimulating Hormone / Q000235:genetics / Q000378:metabolism*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010024:Osteoporosis / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011962:Receptors, FSH / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004967:Estrogens; D016328:NF-kappa B; D021122:Protein Subunits; D011962:Receptors, FSH; D005640:Follicle Stimulating Hormone; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051960:GTP-Binding Protein alpha Subunit, Gi2