In vitro binding of progesterone to receptors in the human endometrium and the myometrium

High affinity, low capacity progesterone binding receptors have been identified in the cytosol fractions of the human endometrium and the myometrium. The endometrial and the myometrial progesterone binding proteins had sedimentation coefficients of 4.5 S and 4.1 S, respectively. Analysis of the bound steroids revealed that, along with progesterone, small amounts of its metabolites (20alpha-hydroxy-4-pregnene-3-one, 5alpha-pregnane-3,20-dione, 5alpha-pregnane-20alpha-ol-3-one) were also bound to the receptor proteins. Among the steroids studied for ligand specificity, 5alpha-pregnane-3,20-dione showed the highest competition for progesterone binding sites. Progestational steroids, like chlormadinone acetate and norgestrel, did not compete for the progesterone receptors. The endometrial and the myometrial progesterone binding receptors were thermolabile and protein in nature. The molecular weight of the endometrial progestrone binding protein was about 60,000-67,000 with a molecular (Stokes) radius of 33 A and the frictional ratio of 1.26. The myometrial progesterone binding protein had a molecular weight of 56,000-58,000 with a molecular (Stokes) radius of 31 A and a frictional ratio of 1.23. The binding of corticosterone to the myometrial cytosol was only 22-34%, whereas with progesterone it was 70-95%. A study of the immunoabsorption of the plasma proteins from the endometrial and the myometrial cytosol suggested the presence of specific progesterone binding receptors in the cytosol that were different to plasma proteins. The association constant of progesterone for the endometrial progesterone receptor was 1.9 x 10(9) M(-1) and for the myometrial progesterone receptor it was 1.4 x 10(9) M(-1), values that are higher than the association constant of progesterone for corticosteroid binding globulin, which is 7 x 10(8) M(-1). The evidence suggested that the human endometrial and the myometrial progesterone binding proteins are different to the corticosteroid-binding globulin.