Regulation of primary response and specific genes in adrenal cells by peptide hormones and growth factors

Abstract

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 β1 (TGFβ1), on the mRNA levels of nuclear proto-oncogenes of the Fos and Jun families and on the mRNA levels of genes expressed in BAC coding for ACTH and AT1 receptors, cytochrome P450scc and P450 17α and 3β-hydroxysteroid dehydrogenase (3β-HSD). ACTH and IGF-1 increased c-fos and jun-B mRNA levels early with later increases in the levels of mRNA for the ACTH receptor and the three steroidogenic enzymes, and enhanced steroidogenic responses to both ACTH and Ang-II. In contrast, Ang-II increased mRNA coding for the three proto-oncogenes (c fos, c- jun, and jun-B), decreased those for P450 17α and 3β-HSD, and caused marked homologous and heterologous steroidogenic desensitization. TGFβ1 increased only jun-B mRNA and markedly reduced BAC-differentiated functions and steroidogenic responsiveness to both ACTH and Ang-II. The long-term effects of ACTH on human adrenal fasciculata cells were comparable with those observed in BAC, whereas the long term effects of Ang-II and TGFβ1 were different from those observed in BAC. Whether these species-specific differences are related to a different effect of these factors on proto-oncogene expression is not yet known.