title: Melatonin inhibits glucocorticoid-dependent GR-TIF2 interaction in newborn hamster kidney (BHK) cells.
abstract: The antagonism exerted by melatonin on the glucocorticoid response has been well established, being strongly dependent on the cellular context. Previously, we found that melatonin inhibits glucocorticoid receptor (GR) dissociation from the chaperone hetero-complex and nuclear translocation on mouse thymocytes. Here, by performing confocal fluorescence microscopy and the Number and Brightness assay we show that in newborn hamster kidney cells (BHK21) melatonin neither affects GR nuclear translocation nor GR homodimerization. Instead, co-immunoprecipitation studies suggest that physiological concentrations of melatonin impair GR interaction with the transcriptional intermediary factor 2 (TIF2). This melatonin effect was not blocked by the MT(1)/MT(2) receptor antagonist luzindole. Curiously, luzindole behaved as an antiglucocorticoid per se by impairing the glucocorticoid-dependent MMTV-driven gene expression affecting neither GR translocation nor GR-TIF2 interaction.
authors.affiliation: Departamento de Química Biológica, Universidad de Buenos Aires, Buenos Aires C1428EGA, Argentina.
authors.forename: Diego M
authors.initials: DM
authors.lastname: Presman
authors.forename: Valeria
authors.initials: V
authors.lastname: Levi
authors.forename: Omar P
authors.initials: OP
authors.lastname: Pignataro
authors.forename: Adali
authors.initials: A
authors.lastname: Pecci
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D019281:Dimerization; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D047468:Immunoprecipitation; D008324:Mammary Tumor Virus, Mouse; D008550:Melatonin / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D051958:Nuclear Receptor Coactivator 2 / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014363:Tryptamines / Q000494:pharmacology
chemical_list: D005938:Glucocorticoids; D051958:Nuclear Receptor Coactivator 2; D011965:Receptors, Glucocorticoid; D044094:Receptors, Melatonin; D014363:Tryptamines; C057154:luzindole; D003907:Dexamethasone; D000242:Cyclic AMP; D008550:Melatonin