Estradiol derivatives: Relationship between utero-trophic activity and affinity to cytosol receptor

The affinities of estradiol and its 19 derivatives to cytosol receptors of rabbit uterus in vitro were studied by measuring their abilities to inhibit the binding of [3H]estradiol to the receptors with reference to their utero-trophic activities in premature mice. The utero-trophic activities of 15 estradiol analogs in vivo were roughly parallel to their affinities to the receptors in vitro. The binding of steroids with receptors was dependent upon the aromatic character of the ring A of the steroid structure, the presence of 3 and 17(3-hydroxyl functional group, the trans-configuration of B and C rings, and the hydrophobic characteristics at 11 position of steroid molecule. Any structural or steric changes except 17a-ethynyl substitution resulted in a decrease of steroid affinity to the receptors.