REGULATION OF PRIMARY RESPONSE AND SPECIFIC GENES IN ADRENAL-CELLS BYPEPTIDE-HORMONES AND GROWTH-FACTORS

Using cultured bovine adrenal fasciculata cells (BAC), we investigated the effects of two hormones, corticotropin (ACTH) and angiotensin II (Ang-II) and two growth factors, insulin-like growth factor I (IGF-I) and transforming growth factor beta 1 (TGF beta 1), on the mRNA levels of nuclear proto-oncogenes of the Fos and Jun families and on the mRN A levels of genes expressed in BAC coding for ACTH and AT1 receptors, cytochrome P450scc and P450 17 alpha and 3 beta-hydroxysteroid dehydro genase (3 beta-HSD). ACTH and IGF-1 increased c-fos and jun-B mRNA lev els early with Inter increases in the levels of mRNA for the ACTH rece ptor and the three steroidogenic enzymes, and enhanced steroidogenic r esponses to both ACTH and Ang-II. In contrast, Ang-II increased mRNA c oding for the three proto-oncogenes (cfos, c-jun, and jun-B), decrease d those for P450 17 alpha and 3 beta-HSD, and caused marked homologous and heterologous steroidogenic desensitization. TGF beta 1 increased only jun-B mRNA and markedly reduced BAC-differentiated functions and steroidogenic responsiveness to both ACTH and Ang-II. The long-term ef fects of ACTH on human adrenal fasciculata cells were comparable with those observed in BAC, whereas the long term effects of Ang-II and TGF beta 1 were different from those observed in BAC. Whether these speci es-specific differences are related to a different effect of these fac tors on proto-oncogene expression is not yet known.