GLUCOCORTICOIDS AND NERVE GROWTH-FACTOR DIFFERENTIALLY MODULATE CELL-ADHESION MOLECULE L1 EXPRESSION IN PC12 CELLS

The differential expression of the cell adhesion molecule L1 by chroma ffin cells has recently been suggested to be responsible for the segre gation of chromaffin cells into homotypic catecholaminergic groups in the adrenal gland. The present study was undertaken to test the hypoth esis that glucocorticoids, which increase in the adrenal gland during development, could be responsible for the repression of L1 in adrenerg ic chromaffin cells. PC12 cells were used as the experimental model, a nd relative L1 protein and mRNA levels were examined after treating th e cells with glucocorticoids or NGF. Analysis of western blots indicat ed that glucocorticoids decreased the L1 protein levels by one-half, w hereas NGF increased L1 protein levels similar to 2.3-fold. In additio n, the glucocorticoids inhibited both the NGF induction of the neurite outgrowth and the increase in L1 expression. Analysis of the mRNA lev els by PCR and northern blots indicated that glucocorticoids reduced t he L1 mRNA, whereas NGF increased the level of L1 mRNA. Maximal inhibi tion of L1 expression was observed at concentrations of 10(-7) M dexam ethasone, and the decrease occurred during the second day of treatment . The effects of dibutyryl cyclic AMP and phorbol ester on the glucoco rticoid and NGF regulation of L1 protein were also examined, This is t he first report indicating that L1 expression can be downregulated by glucocorticoids, The results support the hypothesis that during develo pment the repression of L1 in adrenergic chromaffin cells may be, in p art, linked to the increase in glucocorticoid levels in the adrenal gl and.