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Coumestrol (Co) (25 μg) administered subcutaneously to 21-day-old rats caused an increase in uterine cytosolic protein, estradiol-17β (E 2 ) receptors and progesterone (P 4 ) receptors. A single dose of 25 μg Co resulted in nuclear retention which was quantitatively less and of shorter duration than that following treatment with 0.125 μg E 2 . Other uterine responses (increases in uterine weight, cytosol protein and P 4  cytosol binding) were also less. When Co was administered in repeated doses over a 4-h period or fed for 3 days, uterine responses were similar to those obtained after treatment with 0.125 μg E 2 . When Co was administered with 0.125 μg E 2  on consecutive days, the uterine responses to E 2  were reduced. In this schedule, Co acted as an antiestrogen presumably by displacing the more effective estrogen from a limited number of nuclear binding sites. Zearalanol (Z) (0.5 μg) given as a single dose was retained in the nucleus for a longer period than E 2  but the uterine responses were slightly less. When Z was given simultaneously with E 2  in a single dose, Z reduced the effects of E 2  on P 4  binding sites and on cytosol protein levels. When given with E 2  on two consecutive days, the estrogenic effects on E 2  and P 4  cytosol binding sites and cytosol protein were reduced. These studies indicate that Co and Z, which are naturally occurring estrogens of plant origin, induce many of the same biological and biochemical responses evoked by E 2 . Co can act as an estrogen and an antiestrogen depending on the schedule of administration. Key words: Phytoestrogens, coumestrol, zearalanol, estrogenic/antiestrogenic effects, uterus, rat

THE ESTROGENIC AND ANTIESTROGENIC EFFECTS OF COUMESTROL AND ZEARALANOL ON THE IMMATURE RAT UTERUS