Effects of dihydrotestosterone on bone biochemical markers in sham and oophorectomized rats.
Evidence exists to suggest that androgens stimulate bone formation in the estrogen-deficient state, however the mechanism of action is unclear. The following study investigates the effect of dihydrotestosterone (DHT) on biochemical markers of bone turnover and calcium homeostasis in sham and oophorectomized (oophx) rats when either vehicle, 40, 80, or 160 mg/kg body weight (bw) DHT were administered at the time of operation or at 15 weeks postoperation. Serum alkaline phosphatase (ALP) increased following DHT administration in sham and oophx rats in all groups (mean ALP +/- SEM [U/l] week 8; sham vehicle, 40 +/- 7; sham 160 mg DHT/kg bw, 72 +/- 5; oophx vehicle, 60 +/- 6; oophx 160 mg DHT/kg bw, 88 +/- 11) (p < 0.001). In contrast, serum osteocalcin was significantly suppressed in oophx rats administered DHT 15 weeks following operation (mean osteocalcin +/- SEM [micrograms/l] week 8; oophx vehicle, 17.6 +/- 3.5; oophx 160 mg DHT/kg bw, 10.5 +/- 1) (p < 0.01). Urine deoxypyridinoline was significantly decreased when DHT was administered 15 weeks postoophorectomy (p < 0.001); however, urine hydroxyproline was not affected by DHT treatment in any group. Urine calcium was decreased by DHT treatment (mean Ca/Cr +/- SEM week 8; sham vehicle, 0.87 +/- 0.13; sham 160 mg DHT/kg bw, 0.24 +/- 0.08; oophx vehicle, 0.68 +/- 0.16; oophx 160 mg DHT/kg bw; 0.45 +/- 0.1) (p < 0.005) which was associated with an increase in the renal tubular reabsorption of calcium (p < 0.05). This study demonstrates the direct effects of DHT on both bone cell activities and the renal handling of calcium.
Mason
R A
RA
Department of Physiology, University of Adelaide, South Australia.
Morris
H A
HA
D000469:Alkaline Phosphatase / Q000097:blood; D000728:Androgens / Q000502:physiology*; D000818:Animals; D015415:Biomarkers; D001862:Bone Resorption; D001842:Bone and Bones / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D003404:Creatinine / Q000097:blood; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D006706:Homeostasis; D015675:Osteocalcin / Q000097:blood; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
D000728:Androgens; D015415:Biomarkers; D013196:Dihydrotestosterone; D015675:Osteocalcin; D003404:Creatinine; D000469:Alkaline Phosphatase; D002118:Calcium