Effects of sex steroids on the development of 7,12-dimethylbenz[a]anthracene-induced mammary dysplasia in neonatally androgenized female rats

Abstract

The development of mammary dysplasia (mastopathia cystica) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in neonatally androgenized female rats was dependent on estrogens, and cystic-type mammary dysplasia developed in rats with a relative or absolute excess of estrogens. At 2 days of age, 137 female rats were neonatally androgenized by single subcutaneous injections of 1.25 mg testosterone propionate (TP). At 50 days of age, all rats were given 20 mg DMBA by gastric intubation. About one-half of the TP rats were ovariectomized at 78 days of age. Rats in test groups were given daily intramuscular injections of 10 micrograms 17 beta-estradiol (E) or 4 mg progesterone (P) for 228 days starting from 78 days after birth. In all TP rats, corpora lutea were absent in the ovaries. the incidence of mammary dysplasia in TP rats was 89.7%. Ovariectomy (OVEX) of TP rats induced a significant and marked decrease in the incidence of mammary dysplasia (3.7%). In TP rats with OVEX, a high incidence of mammary dysplasia was found in those given E (95.7%) but not in those given P (0%). The incidences of cystic-type mammary dysplasia in TP rats, TP rats with E, TP rats with OVEX and E and TP rats with P were 65.5, 86.7, 91.3 and 0%, respectively.