Steroid-binding proteins of the mammary gland and their clinical significance in breast cancer.
Differentiation and development of the mammary gland are influenced by estrogens, glucocorticoids, and progesterone. Specific binding sites for each of these classes of steroid hormones have been characterized in vivo and in cell-free preparations of lactating mammary gland of the rat. These properties were compared with those of steroid-binding proteins in the R3230AC and dimethylbenz[a]anthracene-induced mammary tumors of the rat and of human breast carcinomas. The binding components that were protein in nature were more concentrated in tissue from lactating than from virgin or pregnant rats. The steroid-binding capacities of mammary tumors were highly variable. Using a dextran-coated charcoal procedure, the rate constants of 3H-ligand association with specific binding sites were temperature dependent. Ligand specificity indicated that [3H]estradoil-17beta(3H-E) binding was inhibited only by estrogens, whereas [3H]triamcinolone acetonide (3 H-TA) was blocked by glucocorticoid/s and progesterone. Likewise, [3H]progesterone (3H-P) binding was inhibited by progestins and certain glucocorticoids. Incubation of minced mammary gland with 3H-steroid in the presence and absence of unlabeled competitor demonstrated specific binding sites in cytoplasm that were translocated to nuclei in a tempreature-dependent fashion. Using a steroid-exchange procedure both DEX and TA inhibited 3H-P binding to exchangeable sites that were loaded previously with unlabeled progesterone. These data suggest that certain glucocorticoid and progesterone binding sites were translocated simultaneously to nuclei. Administration in vivo of either 3H-E or 3H-TA indicated binding in cytoplasm and subsequent translocation to nuclei.
D000818:Animals; D001665:Binding Sites; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D004355:Drug Stability; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008321:Mammary Glands, Animal / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011960:Receptors, Estrogen; D013256:Steroids / Q000378:metabolism*
D004967:Estrogens; D005938:Glucocorticoids; D008024:Ligands; D011506:Proteins; D011956:Receptors, Cell Surface; D011960:Receptors, Estrogen; D013256:Steroids; D011374:Progesterone