Displacement of 17β-Estradiol from Uterine Receptor Sites by an Estrogen Antagonist

Abstract

Summary

A potent nonsteroidal estrogen antagonist (CN-55,945-27) was found to displace previously bound radioactive 17β-estradiol from the uterus when added to an incubation medium containing uterine horns obtained from intact rats or when administered by gavage to ovariectomized rats. In vitro, this phenomenon was indicated by a significant decrease in the uterine estradiol-4-¹⁴C with a concomitant and progressive increase in the level of radioactivity within the medium during a 3-hour incubation period. Similar results were obtained in vitro when nonradioactive 17β-estradiol was incubated with uteri obtained from rats previously treated with 17β-estradiol-4-¹⁴C in vivo. When CN-55,945-27 was given orally to rats injected subcutaneously 6 hours previously with 17β-estradiol-6,7-³H, it markedly increased the rate of release of estradiol from the uterus over that observed in animals receiving oral vehicle. This effect, as shown by a decrease in uterine estradiol, was significant within 2 hours, increased markedly during the next 6 hours, and continued to nearly complete depletion of uterine estradiol within 16 hours after administration of CN-55,945-27. Uteri obtained from vehicle-treated control rats still contained an appreciable amount of estradiol 16 hours post treatment. These observations indicate that CN-55,945-27 can displace uterine estradiol under physiologic conditions as well as in vitro. Moreover, this action may partially account for the ability of this agent to suppress myometrial activity both in vitro, and in vivo in unanesthetized animals.