Progesterone receptors in mammary gland of the pregnant rat.

Abstract

The characteristics of pregnant rat mammary gland progesteronee receptors have been studied by the use of two synthetic probes, [3H]R5020 (3H-labeled 17 alpha, 21-dimethyl-19-nor-pregn-4,9-diene-3,20-dione) amd [3H]ORG 2058 (3H-labeled 16 alpha-ethyl-21-hydroxy-19-nor-pregn-4-ene-3,20-dione). [3H] ORG 2058 bound with high affinity (Kd at 4 C, approximately 0.5 nM) to an apparent single class of displaceable sites, with a hierarchy of competition as follows: ORG 2058 greater than R5020 greater than or equal to progesterone greater than dexamethasone. In contrast, [3H]R5020 showed binding in mammary gland cytosols which was nonlinear with protein concentration, of intermediate affinity (Kd at 4 C, approximately 5 nM), and poorly displaced by nonradioactive R5020; the hierarchy of competitors was R5020 greater than progesterone greater than dexamethasone = ORG 2058. Parallel studies in rat uterine cytosols showed both [3H]ORG 2058 and [3H]R5020 to bind with high affinity to an apparently identical class of sites; the hierarchy of competition for both was ORG 2058 greater than or equal to R5020 greater than progesteron greater than dexamethasone. We conclude that in pregnant rat mammary gland, as opposed to rat uterus and other tissues, R5020 is unsuitable as a progesterone receptor probe; however, the affinity, capacity, ad specificity characteristics of progesterone receptors in this tissue can be described by the use of ORG 2058.