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

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Abstract
Coumestrol (Co) (25 μg) administered subcutaneously to 21-day-old rats caused an increase in uterine cytosolic protein, estradiol-17β (E2) receptors and progesterone (P4) 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 E2. Other uterine responses (increases in uterine weight, cytosol protein and P4 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 E2. When Co was administered with 0.125 μg E2 on consecutive days, the uterine responses to E2 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 E2 but the uterine responses were slightly less. When Z was given simultaneously with E2 in a single dose, Z reduced the effects of E2 on P4 binding sites and on cytosol protein levels. When given with E2 on two consecutive days, the estrogenic effects on E2 and P4 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 E2. 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