Differential effects of estrogen metabolites on bone and reproductive tissues of ovariectomized rats

被引:59
作者
Westerlind, KC
Gibson, KJ
Malone, P
Evans, GL
Turner, RT
机构
[1] AMC, Ctr Canc Res, Denver, CO 80214 USA
[2] Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA
关键词
D O I
10.1359/jbmr.1998.13.6.1023
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The effects of 17 beta-estradiol and the important estrogen metabolites, 2-hydroxyestrone (2-OHE1) and 16 alpha-hydroxyestrone (16 alpha-OHE1) on bone, mammary gland, and uterine histology, and on blood cholesterol were investigated in ovariectomized growing rats. Rats were treated with 200 mu g/kg of body weight/day of each of the test compounds for 3 weeks, Ovariectomy resulted in uterine and mammary gland atrophy, increased body weight, bone turnover and tibia growth, and hypercholesterolemia. 17 beta-estradiol treatment prevented these changes, with the exception that this high dose of estrogen did not prevent hypercholesterolemia. 2-OHE1 had no effect on any of the measurements. 16 alpha-OHE1 resulted in bone measurements that did not differ from the 17 beta-estradiol-treated rats and prevented the increase in serum cholesterol, In contrast, 16 alpha-OHE1 resulted in increases in uterine weight, uterine epithelial cell height, and mammary gland cell proliferation that were significantly less than the 17 beta-estradiol treatment. These findings demonstrate that 16 alpha-hydroxylation of estrone results in tissue-selective estrogen agonistic activity, whereas 2-hydroxylation resulted in no measured activity. Furthermore, they suggest that factors that modulate the synthesis of these metabolites could selectively influence estrogen target tissues.
引用
收藏
页码:1023 / 1031
页数:9
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