RELEVANCE OF C-FOS PROTOONCOGENE INDUCTION FOR THE STEROIDOGENIC RESPONSE TO ACTH, DCAMP AND PHORBOL ESTER IN ADRENOCORTICAL-CELLS

We previously reported that ACTH, but not dibutyryl cAMP, rapidly indu ces the c-fos proto-oncogene in Y-1 adrenocortical cells. Here we show that PMA induces c-fos with similar kinetics when compared with ACTH (0.5-1 h peak) but reaches only 60% of the maximal ACTH induction and dcAMP is a weak c-fos inducer (15% of ACTH). However, combination of P MA and dcAMP has a synergistic effect leading to maximal c-fos inducti on. c-fos expression may play a role in the RNA synthesis-dependent co rticosteroidogenesis response and/or growth regulation by ACTH. We als o show that, in contrast to dcAMP, PMA is a poor steroidogenesis stimu lator (15 to 17% of maximum ACTH-stimulated level), its activity being completely dependent on RNA synthesis. Combination of dcAMP and PMA y ields an additive steroidogenesis stimulation, an effect that is also dependent on RNA synthesis. Although no strict correlation was found b etween c-fos induction and early steroidogenesis stimulation, particul arly with respect to cAMP derivatives, the results suggest that a PKC pathway is likely to cooperate with the classical cAMP-PKA pathway in adrenal cells' RNA-dependent steroidogenesis.