EFFECT OF AN OESTROGEN ANTAGONIST, CI-628, AND OESTRADIOL ON POST-PARTUM INVOLUTION AND COLLAGEN BREAKDOWN OF THE RAT UTERUS

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Abstract
Female albino rats, 16 days pregnant, were studied. The mean body wt of the animals shortly after parturition was 290 g. Estradiol-17.beta. and CI-628 (1-[2-(p-[.alpha.-(p-methoxyphenyl)-.beta.-nitrostyryl]phenoxy)ethyl]pyrrolidine monocitrate) were administered separately by i.p. injection. Daily administration commenced within 1-6 h of parturition. Control rats received saline injections only. A further group of rats received no treatment, but were separated from their pups shortly after birth to provide a non-nursing group. At the completion of 4 days of involution the uteri were removed. Control values at 4 days post partum represent almost complete involution of the uterus. Treatment with 100 .mu.g estradiol/day produced a striking inhibition (55%) of collagen breakdown and a smaller inhibition (25%) of weight loss. Adding 10 mg CI-628 to the dose of 100 .mu.g estradiol produces a significant antagonism of the estradiol effect. Both wet weight and hydroxyproline are considerably reduced (P = 0.001) in the direction of the control values. Less striking, but still highly significant, effects were produced by 10 .mu.g estradiol/day. Again CI-628 at a level of 10 mg/day reduced the effects of 10 .mu.g estradiol significantly (P = 0.001). A dose of 1 mg CI-628/day had a smaller antagonistic effect than 10 mg when administered with 10 .mu.g estradiol (P = 0.05 for weight and P = 0.02 for hydroxyproline, comparing 10 mg CI-628 in the presence of 10 .mu.g estradiol).

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