Relative binding affinity of various progestins and antiprogestins to a rabbit myometrium receptor

Relative binding affinity (RBA) of various progestins and antiprogestins to a cytoplasmic receptor prepared from the myometrium of estrogenized immature female rabbits was investigated. The cytosol was incubated with tritiated promegestone (3H-R5020) in the presence of various concentrations of non-radioactive promegestone (R5020) as standard on the one hand, and several progestins and antiprogestins on the other hand. The incubate was subjected to isoelectric focusing in slabs of polyacrylamide gel and the bound radioactivity in the peak of the receptor was measured, RBA was expressed as a percentage given by the ratio of those concentrations of R5020 and the compound tested which were required for a 50% displacement of 3H-R5020. The RBA's of the progestins tested were in the following order: R5020 greater than norethisterone greater than levonorgestrel greater than progesterone greater than medroxyprogesterone acetate. There was practically no binding to dextronorgestrel, cortisol, testosterone, and estradiol. In the group of antiprogestins, there were no significant differences in the RBA of the compounds RU 486, RU 42633 (monodemethyl derivative of RU 486) and ZK 98.734. Another two derivatives of RU 486, RU 42848 (didemethyl) and RU 42698 (propargyl), had lower RBA's than RU 486. Two 13,17-stereoisomers related to the above antiprogestins (i.e. compounds ZK 98.299 and ZK 115.716) exhibited a decreased RBA in comparison with the compound ZK 98.734.