Graduate Thesis Or Dissertation
 

Effects of chronic coumestrol administration on female rats

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  • The effects of coumestrol on the uterine weight, uterine fluid imbibition, uterine nucleic acid content, adrenal weight and body weight of female rats were studied. Daily doses of 20 micrograms of coumestrol per 0.1cc propylene glycol were administered subcutaneously to spayed rats following a seven day recovery period, for durations varying from zero to 123 days. Groups treated with 0.1cc propylene glycol and estradiol 17-β at 0.1 microgram per 0.1cc propylene glycol were also run for comparable studies, for periods varying from 48 to 123 days. The results on the chronic effects of estradiol 17-β confirmed that of Rinard (1963). Coumestrol was 0.13 times as active as estradiol 17-β in promoting uterine growth, but its ability to cause fluid imbibition was nearly the same as estradiol 17-β at 123 days. Coumestrol stimulated protein synthesis and inhibited adrenal growth, while estradiol 17-β had the opposite effects. There was a transitional period of coumestrol action at about the 48th day of treatment. The estrogenic properties of coumestrol were not fully expressed until after 100 days of treatment. The animals responded to propylene glycol with marked increase in uterine weight, uterine fluid imbibition, and the RNA/DNA ratio, with no significant changes in the adrenal weight from the 48th day. Animals treated with coumestrol, estradiol 17-β and propylene glycol had a slower rate of growth, which resulted in the animals weighing 30 to 50 grams less than the castrate controls. Upon gross histological examination, tumorigenic and pyometric conditions were found in animals chronically treated with estradiol and propylene glycol, but not in those treated with coumestrol. The effects of coumestrol, estradiol 17-β and propylene glycol on the uterine cellular mitotic rate, cellular permeability, protein synthesis and adrenal metabolism in the animals were discussed.
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