EFFECTS OF OVARIECTOMY AND ESTROGEN ON THE SERUM LEVELS OF INSULIN-LIKE GROWTH-FACTOR-I AND INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3

To determine the effects of ovariectomy and 17 beta-estradiol (E(2)) o n serum IGF-I and its binding proteins, female Sprague-Dawley rats, ag ed 95 days, were divided into four groups. Group 1 was sham-operated; groups 2, 3, and 4 were ovariectomized. Groups 3 and 4 received daily injections of 200 ng (low dose) and 5000 ng (high dose) E(2)/kg body w t./day, respectively and the others were given solvent vehicle. Ovarie ctomy resulted in a significant increase in serum IGF-I (P < 0.001) at 30 and 35 days post-surgery; the increase was prevented in animals th at received low-dose E(2) while high-dose E(2) reduced serum IGF-I lev els below those of the sham-operated controls (P < 0.01). Serum IGF-bi nding proteins (IGFBPs) were determined by IGF-ligand blot analysis, a nd the resulting autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3 bands changed in parallel with serum IGF-I le vels. Ovariectomy increased, low-dose E(2) restored, and high-dose E(2 ) reduced serum IGFBP-3 levels compared to the levels for the sham-ope rated controls. The intensities of binding protein bands smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A Weste rn immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blo t data. The changes in the levels of IGF-I and its binding proteins we re accompanied by ovariectomy-induced increase in osteoblast and osteo clast numbers and loss of cancellous bone that were attenuated by E(2) administration. We conclude that there is a possible role for IGF-I i n the pathogenesis of the increased bone turnover that occurs early in ovarian hormone deficiency.