Pentacyclic analogues of steroids: Interaction of 16 alpha,17 alpha-cyclopentanoprogesterone with proteins of the rat uterus

Using H-3-labeled derivatives, kinetic parameters of specific binding of pr ogesterone (I) and 16 alpha,17 alpha-cyclopentanoprogesterone (II) to prote ins of the uterus soluble fraction in rats were measured. it was shown that their affinities to proteins are comparable (K 10.5 +/- 2.4 and 6.7 +/- 3. 4 nM for (I) and (II), respectively, upon 22 h incubation). The unlabeled c ompound (II) can displace [H-3]progesterone from complexes with the protein with a concentration-independent efficiency corresponding to the ratio of K values for compounds (I) and (II). At the same time, the efficiency of th e unlabeled progesterone in the displacement of [3H]compound (II) from prot ein complexes fell with an increase in the progesterone concentration. The, concentration of high-affinity sites of [H-3]compound (II) exceeded by 1.5 to 2 times the concentration of sites for [H-3]progesterone. Dynamics of di ssociation of proteins complexes of [H-3]progesterone and [H-3]compound (II ) had a two-phase character with a decrease in the dissociation rate consta nts for both phases as the times of exposition of [H-3]ligands to proteins grew. The ratio of slow- and fast-dissociating ligand-receptor complexes wa s-thereby unchanged. These data suggest the presence in the rat uterus solu ble fraction of two types of proteins differing in the capacity to recogniz e the additional five-membered ring D' in the steroid molecule.