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.