TY - JOUR
T1 - Androgens inhibit the osteogenic response to mechanical loading in adult male mice
AU - Sinnesael, Mieke
AU - Laurent, Michaël R
AU - Jardi, Ferran
AU - Dubois, Vanessa
AU - Deboel, Ludo
AU - Delisser, Peter
AU - Behets, Geert J
AU - D'Haese, Patrick C
AU - Carmeliet, Geert
AU - Claessens, Frank
AU - Vanderschueren, Dirk
PY - 2015/2/5
Y1 - 2015/2/5
N2 - Androgens are well known to enhance exercise-induced muscle hypertrophy, however whether androgens also influence bone's adapative 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 in 4 groups: sham-operated, orchidectomized (ORX), testosterone (ORX+T) or non-aromatizable 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<0.05) and DHT (0.17 vs. 0.11 mm sham, p<0.05). However, T partially (+36%) and DHT completely (+10%) failed to exhibit the loading-related increase observed in sham (+107%) and ORX (+131%, all p<0.05) mice. ORX decreased periosteal bone formation (PsBFR), which was restored to sham levels by T and DHT. However, both androgens completely suppressed the loading-related increase in PsBFR. 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 downregulated sclerostin in ORX or T groups. In conclusion, both T and DHT suppress the osteogenic response to mechanical loading.
AB - Androgens are well known to enhance exercise-induced muscle hypertrophy, however whether androgens also influence bone's adapative 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 in 4 groups: sham-operated, orchidectomized (ORX), testosterone (ORX+T) or non-aromatizable 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<0.05) and DHT (0.17 vs. 0.11 mm sham, p<0.05). However, T partially (+36%) and DHT completely (+10%) failed to exhibit the loading-related increase observed in sham (+107%) and ORX (+131%, all p<0.05) mice. ORX decreased periosteal bone formation (PsBFR), which was restored to sham levels by T and DHT. However, both androgens completely suppressed the loading-related increase in PsBFR. 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 downregulated sclerostin in ORX or T groups. In conclusion, both T and DHT suppress the osteogenic response to mechanical loading.
U2 - 10.1210/en.2014-1673
DO - 10.1210/en.2014-1673
M3 - Article (Academic Journal)
C2 - 25654322
SN - 0013-7227
SP - en20141673
JO - Endocrinology
JF - Endocrinology
ER -