3. Melatonin inhibits glucocorticoid-dependent GR-TIF2 interaction in newborn kidney hamster (BHK21) cells

DIEGO M. PRESMAN, VALERIA LEVI, OMAR PIGNATARO AND ADALI PECCI.

MOLECULAR AND CELLULAR ENDOCRINOLOGY.

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2012 vol. 349 p. 214 - 221

0303-7207

The antagonism exerted by melatonin on the glucocorticoid response has been well established, beingstrongly dependent on the cellular context. Previously, we found that melatonin inhibits glucocorticoidreceptor (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 weshow that in newborn hamster kidney cells (BHK21) melatonin neither affects GR nuclear translocationnor GR homodimerization. Instead, co-immunoprecipitation studies suggest that physiological concentrationsof melatonin impair GR interaction with the transcriptional intermediary factor 2 (TIF2). Thismelatonin effect was not blocked by the MT1/MT2 receptor antagonist luzindole. Curiously, luzindolebehaved as an antiglucocorticoid per se by impairing the glucocorticoid-dependent MMTV-driven geneexpression affecting neither GR translocation nor GR–TIF2 interaction.