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

被引:87
|
作者
KALU, DN
ARJMANDI, BH
LIU, CC
SALIH, MA
BIRNBAUM, RS
机构
[1] VET ADM MED CTR,TACOMA,WA 98493
[2] UNIV WASHINGTON,DEPT MED,SEATTLE,WA 98195
来源
BONE AND MINERAL | 1994年 / 25卷 / 02期
关键词
IGF-I; IGFBP-3; OVARIECTOMY; 17-BETA-ESTRADIOL; OSTEOBLASTS; OSTEOCLASTS;
D O I
10.1016/S0169-6009(08)80255-3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
To determine the effects of ovariectomy and 17 beta-estradiol (E(2)) 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) E(2)/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 E(2) while high-dose E(2) 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 E(2) restored, and high-dose E(2) 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 E(2) 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.
引用
收藏
页码:135 / 148
页数:14
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