Induction of hyperplasia and increased DNA content in the uterus of immature rats exposed to coumestrol

Administration of the phyoestrogen coumestrol to ovariectomized rats leads to increases in both wet and dry uterine weights in the absence of an incre ase in uterine DMA content, as reported by Markaverich et at. [Effects of C oumestrol on Estrogen Receptor Function and Uterine Growth in Ovariectomize d Rats. Environ Health Perspect 103:574-581 (1995)]. It was not possible to know if the observed atypical uterotrophic response of coumestrol was asso ciated uniquely with the ovariectomized uterotrophic assay protocol. This q uestion is answered in the present paper. Two experiments are described in which three daily oral gavage administrations of 60 mg/kg/day coumestrol to immature AP rats were followed by assessment of the reproductive tract on the fourth day. In both experiments coumestrol increased uterine fluid cont ent and increased the weights of the uterus, cervix, and vagina. In additio n, bromodeoxyuridine staining of uterine sections enabled confirmation of u terine hyperplasia for the coumestrol-treated animals. In the second experi ment, total uterine DNA was determined; it doubled in the coumestrol-treate d animals. Estradiol benzoate acted as the positive control agent for both of these experiments, and in each case it gave similar responses to those s een for coumestrol. We conclude that the uterotrophic activity of the phyto estrogen coumestrol in the immature intact rat is typical of the activity o f the natural estrogen estradiol.