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Differential Effects of Estrogen Metabolites on Bone and Reproductive Tissues of Ovariectomized Rats
Author(s) -
Westerlind Kim Caroline,
Gibson Kristin J.,
Malone Patricia,
Evans Glenda L.,
Turner Russell T.
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.6.1023
Subject(s) - endocrinology , ovariectomized rat , medicine , estrogen , estrone , biology
The effects of 17β‐estradiol and the important estrogen metabolites, 2‐hydroxyestrone (2‐OHE 1 ) and 16α‐hydroxyestrone (16α‐OHE 1 ) 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‐OHE 1 had no effect on any of the measurements. 16α‐OHE 1 resulted in bone measurements that did not differ from the 17β‐estradiol–treated rats and prevented the increase in serum cholesterol. In contrast, 16α‐OHE 1 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.