| Induction of Hyperplasia and Increased DNA Content in the Uterus of Immature Rats Exposed to Coumestrol John Ashby, Helen Tinwell, Anthony Soames, and John Foster Zeneca Central Toxicological Laboratory, Alderley Park, Macclesfield, Cheshire, United Kingdom Abstract
Administration of the phytoestrogen coumestrol to ovariectomized rats leads to increases in both wet and dry uterine weights in the absence of an increase in uterine DNA content, as reported by Markaverich et al. [Effects of Coumestrol on Estrogen Receptor Function and Uterine Growth in Ovariectomized Rats. Environ Health Perspect 103:574-581 (1995) ]. It was not possible to know if the observed atypical uterotrophic response of coumestrol was associated uniquely with the ovariectomized uterotrophic assay protocol. This question 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 content and increased the weights of the uterus, cervix, and vagina. In addition, bromodeoxyuridine staining of uterine sections enabled confirmation of uterine hyperplasia for the coumestrol-treated animals. In the second experiment, total uterine DNA was determined ; it doubled in the coumestrol-treated animals. Estradiol benzoate acted as the positive control agent for both of these experiments, and in each case it gave similar responses to those seen for coumestrol. We conclude that the uterotrophic activity of the phytoestrogen coumestrol in the immature intact rat is typical of the activity of the natural estrogen estradiol. Key words: coumestrol, DNA synthesis, hyperplasia, immature, rodent, ovariectomized, uterotrophic. Environ Health Perspect 107:819-822 (1999) . [Online 3 September 1999] http://ehpnet1.niehs.nih.gov/docs/1999/107p819-822ashby/ abstract.html Address correspondence to J. Ashby, Zeneca Central Toxicological Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK. Telephone: 44 1625 51 2833. Fax: 44 1625 59 0249. E-mail: John.Ashby@CTL.Zeneca.com We are grateful to B. Markaverich for discussions. Received 27 January 1999 ; accepted 15 June 1999.
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