congresos y reuniones científicas
Melatonin and Luzindole antagonize glucocorticoid receptor activity by different mechanisms
PRESMAN, D.M.; LEVI, V; PECCI A
Los Cocos, Cordoba
Workshop; SISTAM 2010; 2010
The antagonism exerted by the pineal hormone melatonin (MEL) on the glucocorticoid action has been well established; however, its molecular determinants remain still unknown. Previously, we had described that MEL inhibits glucocorticoid receptor (GR) nuclear translocation on mouse thymocytes, most likely by preventing GR-Hsp90 dissociation. Here, we show that in baby hamster kidney cells (BHK21), MEL neither affects GR translocation nor GR nuclear homodimerization, but rather impairs GR interaction with the transcriptional intermediary factor 2 (TIF2). The use of the Mel 1 receptor antagonist Luzindole curiously reveals that this molecule not only fails to block MEL effect but also has potential antiglucocorticoid properties per se. In fact, Luzindole is able to inhibit glucocorticoid-dependent MMTV-driven gene expression without affecting GR translocation or GR-TIF2 interaction. Together, these results reveal that both methoxyindoles antagonize GR activity by different mechanisms and reveal an unexpected diversity on the mechanisms by which MEL can block GR action.