Osteoblast gene expression in rat long bones: Effects of ovariectomy and dihydrotestosterone on mRNA levels

The steroid sex hormones exert major effects on bone formation although the molecular events associated with their activity remain unclear. We have in vestigated the effects of ovariectomy and dihydrotestosterone (DHT) adminis tration to both sham-operated and ovariectomized (ovx) rats on the bone mRN A levels of osteoblast genes. Rats were randomly allocated to either sham o r ovariectomy operations and were administered either vehicle or 40 mg/kg b ody weight DHT by silastic tube implants at the time of operation for 8 wee ks, at which time they were killed and total RNA was extracted from the lon g bones. Northern blot analysis indicated that the mRNA levels of the bone cell genes alpha 1(I) collagen, alkaline phosphatase, osteocalcin, and oste opontin were markedly increased in ovx rats between 6- and 30-fold. DHT adm inistration to ovary-intact, estrogen-sufficient rats increased the mRNA le vels of alpha 1(I) collagen, alkaline phosphatase, osteopontin, and osteoca lcin between 3- and 9-fold. In contrast, DHT did not alter levels of these mRNA species in ovx rats. The data demonstrate that estrogen deficiency inc reased mRNA levels of genes expressed during osteoblast development and sug gest an interplay between estrogen and androgen action in regulating the ex pression of a number of bone cell genes.