Characteristics of progesterone-binding components in neoplastic mammary tissues of the rat.
Characteristics of [3H]progesterone-binding components were studied in cell-free preparations of two hormonally responsive tumors: the R3230AC mammary adenocarcinoma and 9,10-dimethyl-1,2-benzanthracene-induced mammary tumor of the rat. Progesterone-binding macromolecules from cytosols of both mammary neoplasms exhibited sedimentation coefficients of 3.5 to 4.0 S on sucrose gradients of either low or high ionic strength. From Scatchard analyses of titration data, apparent dissociation constants of 4 to 6 X 10(-8) M were determined for ligand-binding protein complexes from either tumor. Specific progesterone-binding capacities varied considerably, ranging from 150 to 650 fmoles/mg of cytosol protein. Optimal binding of [3H]progesterone was reached by 2 to 3 hr at 3 degrees, pH 7.4, and then decreased rapidly. Specificity studies indicated that cortisol, corticosterone, and triamcinolone acetonide competed effectively for [3H]progesterone-binding. This suggested that [3H] progesterone was bound largely to a macromolecule distinct from transcortin, which does not bind glucocorticoids containing 9alpha-fluoro groups. Aldosterone, as well as several androgens and estrogens, were weak competitors of binding except at high concentrations. The nature of the inhibition of progesterone-binding sites by triamcinolone acetonide and corticosterone was competitive. Concurrent titrations of [3H]progesterone and [3H]triamcinolone acetonide-binding sites demonstrated that their binding capacities were similar, considering the relative stabilities of the complexes. These results, which indicated that progesterone and glucocorticoids compete for the same binding site, suggest that these hormones may influence mammary gland differentiation and development by a common mechanism.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000230:Adenocarcinoma / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000728:Androgens / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D003345:Corticosterone / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008024:Ligands / Q000378:metabolism; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface; D014222:Triamcinolone Acetonide / Q000378:metabolism
D000728:Androgens; D004967:Estrogens; D008024:Ligands; D011956:Receptors, Cell Surface; D000450:Aldosterone; D011374:Progesterone; D015127:9,10-Dimethyl-1,2-benzanthracene; D014222:Triamcinolone Acetonide; D003345:Corticosterone; D006854:Hydrocortisone