title: Androgens inhibit the osteogenic response to mechanical loading in adult male mice.
abstract: Androgens are well known to enhance exercise-induced muscle hypertrophy; however, whether androgens also influence bone's adaptive response to mechanical loading remains unclear. We studied the adaptive osteogenic response to unilateral in vivo mechanical loading of tibia in adult male mice in both a long- and a short-term experimental set-up. Mice were divided into four groups: sham operated, orchidectomized (ORX), T (ORX+T), or nonaromatizable dihydrotestosterone (ORX+DHT) replacement. Significant interactions between androgen status and osteogenic response to mechanical loading were observed. Cortical thickness increased by T (0.14 vs 0.11 mm sham, P<.05) and DHT (0.17 vs 0.11 mm sham, P<.05). However, T partially (+36%) and DHT completely (+10%) failed to exhibit the loading-related increase observed in sham (+107%) and ORX (+131%, all P<.05) mice. ORX decreased periosteal bone formation, which was restored to sham levels by T and DHT. However, both androgens completely suppressed the loading-related increase in periosteal bone formation. Short-term loading decreased the number of sclerostin-positive osteocytes in sham, whereas in control fibulas, ORX decreased and T increased the number of sclerostin-positive osteocytes. Loading no longer down-regulated sclerostin in the ORX or T groups. In conclusion, both T and DHT suppress the osteogenic response to mechanical loading.
authors: Division of Clinical and Experimental Endocrinology (M.S., F.J., L.D., G.C., D.V.), Department of Clinical and Experimental Medicine, Molecular Endocrinology Laboratory (M.R.L., V.D., F.C.), Department of Cellular and Molecular Medicine, and Division of Gerontology and Geriatrics (M.R.L.), Department of Clinical and Experimental Medicine, KU Leuven, 3000 Leuven, Belgium; School of Veterinary Science (P.D.), University of Bristol, Bristol BS13NY, United Kingdom; and Laboratory of Pathophysiology (G.J.B., P.C.D.), University of Antwerp, B-2610 Antwerp, Belgium.
authors: Mieke
authors: M
authors: Sinnesael
authors: Michaël R
authors: MR
authors: Laurent
authors: Ferran
authors: F
authors: Jardi
authors: Vanessa
authors: V
authors: Dubois
authors: Ludo
authors: L
authors: Deboel
authors: Peter
authors: P
authors: Delisser
authors: Geert J
authors: GJ
authors: Behets
authors: Patrick C
authors: PC
authors: D'Haese
authors: Geert
authors: G
authors: Carmeliet
authors: Frank
authors: F
authors: Claessens
authors: Dirk
authors: D
authors: Vanderschueren
mesh_terms: D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D013196:Dihydrotestosterone / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009919:Orchiectomy; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology*; D016474:Weight-Bearing / Q000502:physiology*
chemical_list: D000728:Androgens; D013196:Dihydrotestosterone; D013739:Testosterone