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Differential Effects of Estrogen Metabolites on Bone and Reproductive Tissues of Ovariectomized Rats

1998; Oxford University Press; Volume: 13; Issue: 6 Linguagem: Inglês

10.1359/jbmr.1998.13.6.1023

1523-4681

Kim C. Westerlind, Kristin J. Gibson, Patricia Malone, Glenda L. Evans, Russell T. Turner,

Endometrial and Cervical Cancer Treatments

Abstract The effects of 17β-estradiol and the important estrogen metabolites, 2-hydroxyestrone (2-OHE1) and 16α-hydroxyestrone (16α-OHE1) on bone, mammary gland, and uterine histology, and on blood cholesterol were investigated in ovariectomized growing rats. Rats were treated with 200 μg/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. 17β-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. 16α-OHE1 resulted in bone measurements that did not differ from the 17β-estradiol–treated rats and prevented the increase in serum cholesterol. In contrast, 16α-OHE1 resulted in increases in uterine weight, uterine epithelial cell height, and mammary gland cell proliferation that were significantly less than the 17β-estradiol treatment. These findings demonstrate that 16α-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.