Interaction of the selective progesterone 16a, 17a-cyclohex-3'-enoprogesterone agonist with the rat uterus progesterone receptor

Binding of [ 3 H]-16a-cyclohex-3'-enoprogesterone (I) and [ 3 H]-progesterone (II) with soluble fraction proteins of the rat uterus is compared. I specifically reacts with progesterone receptor but not with other proteins. Its affinity to the receptor assessed from K d (11.6+2.0 nM), Kj (15 nM) values and relative competitive'activity (0.89+0.35 and 0.33+0.04 with [ 3 H]-I and [ 3 H]-II, respectively) is just negligibly inferior to the affinity of the natural hormone (K d =6.9+2.6 nM, Kj=8.5 nM, relative competitive activity =1). The dissociation of [ 3 H]-I and [ 3 H]-II complexes with the receptor was biphasic with similar constants of dissociation rate (kf I =1.8x.lO' 5 C' 1 ; кД=4.5*10' 4 C 1 ). Specific features of [ 3 H]-I reaction with the receptor in comparison with [ 3 H]-II are a lesser share of rapidly dissociating [ 3 H]-I complexes and a lower capacity of [ 3 H]-I to prevent the receptor degradation. It is probable that the detected features reflect the differences in the receptor conformation and are associated with the selectivity of I action.