Role of DNA and specific cytoplasmic receptors in glucocorticoid action.
Glucocorticoids induce tyrosine aminotransferase (EC 2.6.1.5) synthesis in cultured rat hepatoma cells. These steroids penetrate the cell membrane and bind to specific cytoplasmic receptor proteins. The resulting complex binds to the nucleus. This nuclear binding has now been studied in a cell-free preparation. The reaction appears to require a temperature-dependent modification of the steroid-receptor complex. There is a fixed number of nuclear sites that are half saturated at a complex concentration of 6 to 24 x 10(-11) M. Treatment with deoxyribonuclease destroys nuclear-binding capacity. The complex also binds to purified HTC cell DNA with characteristics similar to the binding to isolated nuclei, and, as in intact cells, receptors complexed with an anti-inducer steroid bind very poorly to DNA. These data suggest that the nuclear sites for binding steroid-receptor complexes are on the DNA. Since the extent of complex binding to purified DNA exceeds that observed with isolated nuclei, chromosomal proteins may act to restrict binding to certain regions of the DNA. These studies suggest that steroid hormones stimulate the synthesis of specific proteins by affecting the transcription of structural or regulatory genes.
D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002850:Chromatography, Gel; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000494:pharmacology; D003907:Dexamethasone / Q000378:metabolism; D004790:Enzyme Induction; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000378:metabolism; D008113:Liver Neoplasms; D011374:Progesterone / Q000494:pharmacology; D011955:Receptors, Drug; D013696:Temperature; D014316:Tritium; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D004273:DNA, Neoplasm; D005938:Glucocorticoids; D011955:Receptors, Drug; D014316:Tritium; D011374:Progesterone; D003907:Dexamethasone; D014444:Tyrosine Transaminase; D003851:Deoxyribonucleases; D006854:Hydrocortisone