GLUCOCORTICOID RECEPTOR EXPRESSION DURING DIFFERENTIATION OF HUMAN PROMYELOIC LEUKEMIA-CELLS

The human promyeloic leukemia cell line HL-60 can be triggered in cult ure to differentiate into several cell types of the myeloid lineage in response to a variety of chemical stimuli. We used this cell system i n order to investigate the changes in glucocorticoid receptors which o ccur concomitantly with such cellular differentiations. Neutrophilic g ranulocytes obtained by the addition of dimethyl sulfoxide or retinoic acid to the culture medium showed only slight changes in cellular glu cocorticoid receptor levels and receptor-specific mRNA as compared to undifferentiated control cells. Monocytic cells induced by incubation with dihydroxy-vitamin D3 had a moderate increase in receptor hormone- binding activity. However, differentiation toward macrophages by expos ure to phorbol ester resulted in a 5- to 6- fold increase in both cell ular hormone-binding capacity and immunochemically cross-reacting rece ptor protein. An even greater increase in glucocorticoid receptor-spec ific mRNA was observed. These data suggest that the receptor is regula ted at the mRNA level and that de novo receptor synthesis occurs durin g macrophage differentiation, thus making these cells potentially more susceptible to glucocorticoid-induced effects.