Dexamethasone regulates the expression of neuronal properties of a rat insulinoma cell line.
Insulin producing cells of the pancreas (beta cells) and neuronal cells share a large number of similarities. For example, different molecules, thought to be specific of neuronal cells, are expressed by beta cells. 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 treatment decreases the steady state levels of mRNAs coding for both the low- 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 decrease in NGF receptors mRNAs steady state levels was paralleled by a decrease in the number of NGF binding sites as demonstrated after Scatchard analysis. We further focused on the mechanisms by which dexamethasone affects the expression of the low affinity NGF receptor. The effect is countered by the glucocorticoid antagonist RU486, indicating that it is mediated by the glucocorticoid receptor. Finally, the decrease in the low-affinity nerve growth factor receptor mRNA steady state level after dexamethasone treatment is not due to mRNA destabilization but can be rather explained through a change in gene transcription.
Atouf
F
F
INSERM CJF 93-13, Hospital R. Debré, Paris, France.
Tazi
A
A
Polak
M
M
Czernichow
P
P
Scharfmann
R
R
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D007340:Insulinoma; D007381:Intermediate Filament Proteins / Q000096:biosynthesis; D007700:Kinetics; D015735:Mifepristone / Q000494:pharmacology; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010190:Pancreatic Neoplasms; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D007381:Intermediate Filament Proteins; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D015735:Mifepristone; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase