Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus

We have previously reported that low doses of melatonin inhibit apoptosis i n both dexamethasone-treated cultured thymocytes (standard model for the st udy of apoptosis) and the intact thymus. Here we elucidate the mechanism by which this agent protects thymocytes from cell death induced by glucocorti coids. Our results demonstrate an effect of melatonin on the mRNA for antio xidant enzymes in thymocytes, also showing an unexpected regulation by dexa methasone of these mRNA Both an effect of melatonin on the general machiner y of apoptosis and a possible regulation of the expression of the cell deat h related genes bcl-2 and p53 are shown not to be involved, We found melato nin to down-regulate the mRNA for the glucocorticoid receptor in thymocytes (glucocorticoids up-regulate their own receptor). The decrease by melatoni n of mRNA levels for this receptor in IM-9 cells (where glucocorticoids dow n-regulate it) demonstrates that melatonin actually down-regulates glucocor ticoid receptor. These findings allow us to propose the effects of melatoni n on this receptor as the likely mediator of its thymocyte protection again st dexamethasone-induced cell death. This effect of melatonin, given the ox idant properties of glucocorticoids, adds another mechanism to explain its antioxidant effects.