title: Bone turnover across the menopause transition : The role of gonadal inhibins.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Nicks
authors.forename: Tristan W
authors.initials: TW
authors.lastname: Fowler
authors.forename: Nisreen S
authors.initials: NS
authors.lastname: Akel
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Perrien
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Suva
authors.forename: Dana
authors.initials: D
authors.lastname: Gaddy
mesh_terms: 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
chemical_list: D015415:Biomarkers; D007265:Inhibins
references.citation: Trends Mol Med. 2005 Feb;11(2):76-81
references.pmid: 15694870
references.citation: Semin Reprod Med. 2004 Aug;22(3):269-76
references.pmid: 15319829
references.citation: J Clin Endocrinol Metab. 1996 Jul;81(7):2742-5
references.pmid: 8675606
references.citation: J Bone Miner Res. 1999 Apr;14(4):609-15
references.pmid: 10234583
references.citation: Nature. 2000 Mar 23;404(6776):411-4
references.pmid: 10746731
references.citation: J Bone Miner Res. 2008 Feb;23(2):205-14
references.pmid: 17937534
references.citation: Osteoporos Int. 1998;8(3):282-90
references.pmid: 9797914
references.citation: Recent Prog Horm Res. 2002;57:385-409
references.pmid: 12017554
references.citation: J Clin Endocrinol Metab. 1996 Apr;81(4):1401-5
references.pmid: 8636341
references.citation: J Biol Chem. 2001 May 4;276(18):14588-96
references.pmid: 11278442
references.citation: J Biol Chem. 2003 Mar 7;278(10):7934-41
references.pmid: 12493742
references.citation: J Biol Chem. 2008 Mar 21;283(12):7628-37
references.pmid: 18184661
references.citation: J Biol Chem. 1988 Nov 15;263(32):16984-91
references.pmid: 2903157
references.citation: Mol Endocrinol. 2007 Nov;21(11):2713-24
references.pmid: 17636036
references.citation: Endocrinology. 1993 Feb;132(2):725-34
references.pmid: 8425491
references.citation: Novartis Found Symp. 2002;242:247-59; discussion 260-4
references.pmid: 11855691
references.citation: Ann N Y Acad Sci. 2006 Apr;1068:19-25
references.pmid: 16831902
references.citation: J Clin Endocrinol Metab. 1998 Jul;83(7):2266-74
references.pmid: 9661593
references.citation: Endocrinology. 2002 Jan;143(1):74-83
references.pmid: 11751595
references.citation: Endocr Rev. 1994 Feb;15(1):27-39
references.pmid: 8156937
references.citation: J Leukoc Biol. 2002 Aug;72(2):347-52
references.pmid: 12149426
references.citation: J Clin Endocrinol Metab. 1999 Jan;84(1):105-11
references.pmid: 9920069
references.citation: Mol Cell Endocrinol. 2004 Oct 15;225(1-2):29-36
references.pmid: 15451565
references.citation: J Clin Endocrinol Metab. 2006 May;91(5):1848-54
references.pmid: 16449331
references.citation: J Clin Endocrinol Metab. 1996 Sep;81(9):3366-71
references.pmid: 8784098
references.citation: Cell. 2006 Apr 21;125(2):247-60
references.pmid: 16630814
references.citation: Ann N Y Acad Sci. 2004 Dec;1038:142-7
references.pmid: 15838109
references.citation: J Bone Joint Surg Am. 1991 Oct;73(9):1418-28
references.pmid: 1918129
references.citation: Maturitas. 2005 Oct 16;52(2):147-53
references.pmid: 16186077
references.citation: Endocrinology. 2006 Jul;147(7):3462-71
references.pmid: 16601134
references.citation: J Clin Endocrinol Metab. 1997 May;82(5):1522-7
references.pmid: 9141544
references.citation: Recent Prog Horm Res. 2002;57:257-75
references.pmid: 12017547
references.citation: J Clin Endocrinol Metab. 2006 Mar;91(3):885-91
references.pmid: 16368747
references.citation: J Bone Miner Res. 2004 Dec;19(12):1945-54
references.pmid: 15537436
references.citation: Endocr Rev. 2000 Apr;21(2):115-37
references.pmid: 10782361
references.citation: Mayo Clin Proc. 2000 Jan;75 Suppl:S46-50
references.pmid: 10959216
references.citation: Endocrinology. 2007 Apr;148(4):1654-65
references.pmid: 17194739