Binding of Steroids to Progesterone Receptor Proteins in Chick Oviduct and Human Uterus

A number of synthetic and naturally occurring steroids were studied for competitive binding to two progesterone receptors, one in chick oviduct and another in human uterus. The results show a good correlation of relative (to progesterone) binding affinity with progestational activity as measured by subcutaneous Clauberg assay. 17α-Ethynyltestosterone and closely related compounds compete very well in binding to both receptors; 19-nor derivatives show dramatic enhancement of binding affinity to the human receptor. Of the substituted progesterones tested, 21-fluoro- and 6αfluoroprogesterone competed best with progesterone for binding to both receptors. 17α-Acetoxyprogesterone and the substituted 17α-acetoxyprogesterones tested were fairly good competitors for the human receptor but did not compete at all for the chick. The binding data are assessed in terms of structural requirements for formation of a steroid-receptor complex. The data suggest that the receptors are able to modify the mode of binding at ring D to accommodate several different types of C-17 substitution. Of the steroids with reactive halo, thio, diazo or chloromercuri substituents which were tested as possible substrates for affinity labeling of the receptor active site, only 6α- and 6β-bromoprogesterone and 17β-thiol- and 17β-methylthio-4-androsten-3-one competed sufficiently well with progesterone as to be considered good candidates.