Concept evaluation: an assay for receptor-mediated and biochemical antiestrogens using pubertal rats.

ABSTRACT

At present, assessment of chemicals for receptor-mediated antiestrogenic activity involves inhibition of uterine growth stimulated by coadministration of a reference estrogen in either ovariectomized or immature rodents. In the present paper, we describe an alternative assay for both receptor-mediated and biochemical antiestrogens. The assay involves treatment of immature rats from postnatal (pnd) 25 or 26 for either 7 or 14 days and monitors two benchmarks of puberty, the mean day of vaginal opening and the weight of the uterus, that require estrogen activity. The receptor-mediated antiestrogens ZM 189,154 and Faslodex (ICI 182,780), the aromatase inhibitor Arimidex (Anastrozole), and the GnRH inhibitor Antarelix were each effective in preventing uterine growth and in delaying vaginal opening for the course of the experiments. The 5alpha-reductase inhibitor Finasteride was inactive in the assay indicating assay specificity for antiestrogens. Delays in uterine growth were clearly evident in the 7-day experiments, but assessment of vaginal opening required the 14-day protocol. No significant changes in body weight were observed in any of the experiments. It is concluded that the assay holds promise as a simple method of detecting antiestrogens and that it is worthy of further study.