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 (E2) on serum IGF-I and its binding proteins, female Sprague-Dawley rats, aged 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) E2/kg body wt./day, respectively and the others were given solvent vehicle. Ovariectomy 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 that received low-dose E2 while high-dose E2 reduced serum IGF-I levels below those of the sham-operated controls (P < 0.01). Serum IGF-binding proteins (IGFBPs) were determined by IGF-ligand blot analysis, and the resulting autoradiograms quantified by laser densitometry. The intensity of the IGFBP-3 bands changed in parallel with serum IGF-I levels. Ovariectomy increased, low-dose E2 restored, and high-dose E2 reduced serum IGFBP-3 levels compared to the levels for the sham-operated controls. The intensities of binding protein bands smaller than those of IGFBP-3 appeared unchanged by the treatment regimens. A Western immunoblot analysis with IGFBP-3 antiserum confirmed the ligand-blot data. The changes in the levels of IGF-I and its binding proteins were accompanied by ovariectomy-induced increase in osteoblast and osteoclast numbers and loss of cancellous bone that were attenuated by E2 administration. We conclude that there is a possible role for IGF-I in the pathogenesis of the increased bone turnover that occurs early in ovarian hormone deficiency.
Kalu
D N
DN
Department of Physiology, University of Texas Health Science Center, San Antonio 78284-7756.
Arjmandi
B H
BH
Liu
C C
CC
Salih
M A
MA
Birnbaum
R S
RS
D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010006:Osteoblasts / Q000187:drug effects; D010010:Osteoclasts / Q000187:drug effects; D010052:Ovariectomy; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013002:Somatomedins / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D004958:Estradiol; D007334:Insulin-Like Growth Factor I