PEPTIDE-HORMONE AND GROWTH-FACTOR REGULATION OF NUCLEAR PROTOONCOGENES AND SPECIFIC FUNCTIONS IN ADRENAL-CELLS

Among the large number of immediate early genes, nuclear proto-oncogen es of the Fos and Jun families, have been postulated to be involved in the long-term effects of several growth factors on eel differentiatio n and/or multiplication. Since adrenal cell differentiated functions a ppear to be regulated by specific hormones and growth factors, the eff ects of these factors on proto-oncogene mRNA levels were analysed in b ovine adrenal fasciculata cells (BAC) in culture. Corticotropin (ACTH) and insulin-like growth factor I increased c-fos and jun-B mRNA, but had no effect on c-jun mRNA and these early changes were associated wi th a later increase in BAC specific function [ACTH receptors, cytochro me P450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) ] and an enhanced steroidogenic responsiveness to both ACTH and angiot ensin-II (A-II). On the other hand, A-II increased the three proto-onc ogene (c-fos, c-jun and jun -B) mRNAs, induced a decrease of P450 17 a lpha and 3 beta-HSD and caused a marked homologous and heterologous (A CTH) densitization. Transforming growth factor beta(1) which only incr eased jun-B mRNA, markedly reduced BAC differentiated functions and th e steroidogenic responsiveness to both ACTH and A-II. Thus, it is post ulated that the proto-oncoproteins encoded by the immediate early gene s may play a role in the long-term effects of peptide hormones and gro wth factors on BAC differentiated functions.