title: Inhibin A is an endocrine stimulator of bone mass and strength.
abstract: Gonadal function plays a major role in bone homeostasis. It is widely held that the skeletal consequences of hypogonadism are solely due to a loss of sex steroids; however, increases in bone turnover begin during perimenopause before decreases in serum estradiol levels. These data and our demonstration that inhibins acutely regulate bone cell differentiation in vitro led us to test whether inhibin A (InhA) regulates bone mass in vivo. Using a transgenic model of inducible human InhA expression, InhA increased total body bone mineral density, increased bone volume, and improved biomechanical properties at the proximal tibia in intact mice and also prevented the loss of BMD and bone volume and strength associated with gonadectomy at both the spine and proximal tibia. In addition, InhA increased mineral apposition rate, double-labeled surface, and serum osteocalcin levels in vivo and osteoblastogenesis ex vivo without affecting osteoclast number or activity. Together these results demonstrate novel stimulatory effects of InhA on the skeleton in vivo. These studies provide in vivo evidence demonstrating that gonadal factors other than sex steroids play an important role in regulating bone mass and strength and, combined with our previous clinical data, suggest that gonadal InhA may be a component of the normal endocrine repertoire that regulates bone quality in both the axial and appendicular skeleton.
authors.affiliation: Department of Physiology and Biophysics, Center for Orthopaedic Research, University of Arkansas for Medical Sciences, 4301 West Markham, Slot 505, Little Rock, Arkansas 72205, USA.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Perrien
authors.forename: Nisreen S
authors.initials: NS
authors.lastname: Akel
authors.forename: Paul K
authors.initials: PK
authors.lastname: Edwards
authors.forename: Adam A
authors.initials: AA
authors.lastname: Carver
authors.forename: Manali S
authors.initials: MS
authors.lastname: Bendre
authors.forename: Frances L
authors.initials: FL
authors.lastname: Swain
authors.forename: Robert A
authors.initials: RA
authors.lastname: Skinner
authors.forename: William R
authors.initials: WR
authors.lastname: Hogue
authors.forename: Kristy M
authors.initials: KM
authors.lastname: Nicks
authors.forename: Tyler M
authors.initials: TM
authors.lastname: Pierson
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Suva
authors.forename: Dana
authors.initials: D
authors.lastname: Gaddy
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000235:genetics; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects; D002478:Cells, Cultured; D019245:Compressive Strength / Q000187:drug effects; D005260:Female; D006801:Humans; D007265:Inhibins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015735:Mifepristone / Q000008:administration & dosage; D009919:Orchiectomy; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism
chemical_list: C422362:inhibin A; D015735:Mifepristone; D007265:Inhibins