Peptide hormone and growth factor regulation of nuclear proto-oncogenes and specific functions in adrenal cells |
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Authors: | Isabelle Viard, Armelle Penhoat, Rachida Ouali, Langlois Dominique, B geot Martine,Saez Jos M. |
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Affiliation: | INSERM-INRA U 307, Hôpital Debrousse, 29 Rue Soeur Bouvier, 69322, Lyon Cédex 05, France |
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Abstract: | Among the large number of immediate early genes, nuclear proto-oncogenes of the Fos and Jun families, have been postulated to be involved in the long-term effects of several growth factors on cell differentiation and/or multiplication. Since adrenal cell differentiated functions appear to be regulated by specific hormones and growth factors, the effects of these factors on proto-oncogene mRNA levels were analysed in bovine 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 with a later increase in BAC specific function [ACTH receptors, cytochrome P 450 17) and 3β-hydroxysteroid dehydrogenase (3β-HSD)] and an enhanced steroidogenic responsiveness to both ACTH and angiotensin-II (A-II). On the other hand, A-II increased the three proto-oncogene (c-fos, c-jun and jun-B) mRNAs, induced a decreased of P 450 17 and 3β-HSD and caused a marked homologous and heterologous (ACTH) densitization. Transforming growth factor β1 which only increased jun-B mRNA, markedly reduced BAC differentiated functions and the steroidogenic responsiveness to both ACTH and A-II. Thus, it is postulated that the proto-oncoproteins encoded by the immediate early genes may play a role in the long-term effects of peptide hormones and growth factors on BAC differentiated functions. |
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