ESTROGEN MODULATES THE MESSENGER-RNA LEVELS FOR CANCELLOUS BONE PROTEIN OF OVARIECTOMIZED RATS

This study was undertaken to examine the effects of ovariectomy and 17 beta-estradiol (E(2)) on the gene expression of type 1 collagen, oste ocalcin and the protooncogen, c-myc, in cancellous bone. Female Spragu e-Dawley rats, aged 95 days, were divided into 4 groups. Group 1 was s ham operated and Groups 2-4 were ovariectomized. Groups 3 and 4 receiv ed daily injections of 160 ng and 1600 ng E(2)/kg body weight, respect ively. Groups 1 and 2 received the solvent vehicle. All animals were s acrificed after 14 days. The femurs were dissected out and cancellous bone scraped from the distal metaphysis. RNA was isolated from the can cellous bone, immobilized on filters or size-fractionated by agarose g el electrophoresis and adsorbed on filters which were then hybridized with specific cDNA probes. Ovariectomy resulted in a significant incre ase in the mRNAs of type 1 collagen, osteocalcin and c-myc. The increa se was suppressed in animals that received 17 beta-estradiol injection s. In addition, ovariectomy caused the expected decrease in cancellous bone in the proximal tibia and increased osteoclast and osteoblast nu mbers. The ovariectomy-induced changes were prevented by 17 beta-estra diol administration. These findings suggest that the lack of ovarian h ormones shortly after ovariectomy up-regulates and estrogen administra tion down-regulates the expression of important cancellous bone matrix proteins as well as the protooncogen, c-myc.