Effects of dihydrotestrone on osteoblast gene expression in osteopenic ovariectomized rats.
Androgens stimulate bone formation, however, the precise mechanism of androgen action on osteoblasts remains to be elucidated. In this study, we defined the expression profile of osteoblast genes in ovariectomized rats with established osteopenia and their response to treatment with dihydrotestosterone (DHT). Twenty-four, 8-month-old female Sprague-Dawley rats were ovariectomized (ovx) and were administered vehicle, 40 mg, 80 mg, or 160 mg/kg body weight DHT at 15-weeks post-ovariectomy for 14 weeks. Alkaline phosphatase (ALP) messenger ribonucleic acid (mRNA) levels were increased at 29-weeks post-ovariectomy compared with preoperative rats (P < 0.05). In contrast, osteopontin and osteocalcin mRNA levels were unchanged. Treatment of osteopenic ovx rats with DHT for 14 weeks suppressed the ovariectomy-induced increase in ALP (P < 0.05) mRNA levels, independent of dose. These data suggest that androgens may act to inhibit the stimulation of the early stages of osteoblast development that occurs in the absence of estrogen and in states of low bone turnover.
Davey
Rachel A
RA
Hanson Institute, Adelaide, South Australia, Australia. r.davey@unimelb.edu.au
Morris
H A
HA
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism*; D000728:Androgens / Q000494:pharmacology; D000818:Animals; D001851:Bone Diseases, Metabolic / Q000188:drug therapy / Q000503:physiopathology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D000090602:Collagen Type I, alpha 1 Chain; D013196:Dihydrotestosterone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D053495:Osteopontin; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000502:physiology
D000728:Androgens; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D012333:RNA, Messenger; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D013196:Dihydrotestosterone; D015675:Osteocalcin; D053495:Osteopontin; D013739:Testosterone; D000469:Alkaline Phosphatase