Screening of anti-progestins using in vitro human uterine progesterone receptor assay system

Abstract

An in vitro receptor assay system is developed as a method for screening new anti-progestins using human uterine progesterone receptors. Sixty-two (steroidal and non-steroidal) compounds including the suspected anti-progestins obtained from various pharmaceutical companies were screened. Some synthetic progestins were found to be good agonists which revealed high relative binding affinity (RBA) for uterine progesterone receptors. The metabolites of progesterone and norethisterone, showed comparatively poor binding affinity. Of the 30 suspected anti-progestins studied, R 2323, STS 557 and RMI 14156 showed encouraging results with considerably high binding affinity. The results showed that the steric configuration, hydrophobicity, hydrophilicity. spatial requirements, optimal contact, steric hindrance etc. are some of the important factors determining the relative binding affinity of a compound. Although the uterine progesterone receptor concentration varied during the menstrual cycle, being as high as 1200 fmol/mg protein during the late proliferative and about 300 fmol/mg protein during the secretory phase, the affinity for different compounds was identical (with a good correlation coefficient of 0.97). The method developed is simple and specific for screening of a compound as anti-progestin at the human uterine progesterone receptor level.