Regulation of c-fos expression by IGF-I in bovine chromaffin cells: desensitization following cholinergic activation.
Effects of insulin-like growth factor I on the expression of the immediate-early gene c-fos in adrenomedullary tissue were assessed in bovine chromaffin cells in primary culture. The expression of c-fos mRNA and FOS protein were studied by Northern blot and immunofluorescence microscopy. IGF-I induced c-fos mRNA expression in a dose-dependent manner, reaching a maximum at 10-100 nM after 30 min incubation. Expression of FOS protein exhibited a transient time course peaking after 60-90 min. Repeated exposures to IGF-I attenuated c-fos transcriptional activity with a temporal coincidence of 90% repression and maximal FOS protein levels. Exposure to the cholinergic agonist carbachol or the protein tyrosine phosphatase inhibitor orthovandate also induced c-fos transcription. Both agents caused repression in c-fos gene activation induced by either IGF-I, carbachol or orthovanadate. This suggested autoinhibition of c-fos transcription by FOS protein synthesized during the initial stimulation period. These data are consistent with IGF-I stimulating c-fos gene activation in the adrenal medulla and show that c-fos expression can be negatively regulated by temporal neural and hormonal stimulation.
Skar
R
R
Department of Physiology, University of Bergen, Norway.
Larsen
T H
TH
Serck-Hanssen
G
G
D000313:Adrenal Medulla / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D002217:Carbachol / Q000494:pharmacology*; D002417:Cattle; D002838:Chromaffin System / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D008856:Microscopy, Fluorescence; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation; D014638:Vanadates / Q000494:pharmacology
D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D014638:Vanadates; D007334:Insulin-Like Growth Factor I; D002217:Carbachol