Ma. Salih et al., ESTROGEN MODULATES THE MESSENGER-RNA LEVELS FOR CANCELLOUS BONE PROTEIN OF OVARIECTOMIZED RATS, Bone and mineral, 23(3), 1993, pp. 285-299
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.