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 chromaffin cells has recently been suggested to be responsible for the segregation of chromaffin cells into homotypic catecholaminergic groups in the adrenal gland. The present study was undertaken to test the hypothesis that glucocorticoids, which increase in the adrenal gland during development, could be responsible for the repression of L1 in adrenergic chromaffin cells. PC12 cells were used as the experimental model, and relative L1 protein and mRNA levels were examined after treating the cells with glucocorticoids or NGF. Analysis of western blots indicated that glucocorticoids decreased the L1 protein levels by one-half, whereas NGF increased L1 protein levels approximately 2.3-fold. In addition, the glucocorticoids inhibited both the NGF induction of the neurite outgrowth and the increase in L1 expression. Analysis of the mRNA levels by PCR and northern blots indicated that glucocorticoids reduced the L1 mRNA, whereas NGF increased the level of L1 mRNA. Maximal inhibition of L1 expression was observed at concentrations of 10(-7) M dexamethasone, and the decrease occurred during the second day of treatment. The effects of dibutyryl cyclic AMP and phorbol ester on the glucocorticoid and NGF regulation of L1 protein were also examined. This is the first report indicating that L1 expression can be down-regulated by glucocorticoids. The results support the hypothesis that during development the repression of L1 in adrenergic chromaffin cells may be, in part, linked to the increase in glucocorticoid levels in the adrenal gland.
Grant
N J
NJ
Institut Nationale de la Santé, Biologie de la Communication Cellulaire, Strasbourg, France.
Claudepierre
T
T
Aunis
D
D
Langley
K
K
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology*; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins / Q000187:drug effects / Q000235:genetics*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D015816:Cell Adhesion Molecules, Neuronal; D005938:Glucocorticoids; D039841:Leukocyte L1 Antigen Complex; D008562:Membrane Glycoproteins; D009414:Nerve Growth Factors; D010703:Phorbol Esters; D012333:RNA, Messenger; D003994:Bucladesine; D003907:Dexamethasone; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C