DEXAMETHASONE REGULATES THE EXPRESSION OF NEURONAL PROPERTIES OF A RAT INSULINOMA CELL-LINE

Insulin producing cells of the pancreas (beta cells) and neuronal cell s share a large number of similarities. For example, different molecul es, thought to be specific of neuronal cells, are expressed by beta ce lls. The factors regulating the expression of these molecules in beta cells are poorly understood. In the present work, we have studied the effect of dexamethasone, a synthetic glucocorticoid, on the expression of three different neuronal traits expressed by INS-1 cells, a highly differentiated beta cell line. We demonstrate that dexamethasone trea tment decreases the steady slate levels of mRNAs coding for both the l ow-and the high-affinity NGF receptors and of mRNA coding for NF-H, an intermediate neurofilament specific of neurons. This effect was time- dependent, the decrease being detectable after 4-8 h treatment. The de crease in NGF receptors mRNAs steady state levels was paralleled by a decrease in the number of NGF binding sites as demonstrated after Scat chard analysis. We further focused on the mechanisms by which dexameth asone affects the expression of the low affinity NGF receptor. The eff ect is countered by the glucocorticoid antagonist RU486, indicating th at it is mediated by the glucocorticoid receptor. Finally, the decreas e in the low-affinity nerve growth factor receptor mRNA steady state l evel after dexamethasone treatment is not due to mRNA destabilization but can be rather explained through a change in gene transcription.