Peptide hormone and growth factor regulation of nuclear proto-oncogenes and specific functions in adrenal cells.
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 P450 17 alpha) and 3 beta-hydroxysteroid dehydrogenase (3 beta-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 decrease of P450 17 alpha and 3 beta-HSD and caused a marked homologous and heterologous (ACTH) densitization. Transforming growth factor beta 1 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.
Viard
I
I
INSERM-INRA U 307, Hôpital Debrousse, Lyon, France.
Penhoat
A
A
Ouali
R
R
Langlois
D
D
Bégeot
M
M
Saez
J M
JM
D000311:Adrenal Glands / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002417:Cattle; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos; D016758:Genes, jun; D006133:Growth Substances / Q000494:pharmacology*; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019311:Staurosporine; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology
D000470:Alkaloids; D006133:Growth Substances; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D014268:Trifluoperazine; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D019311:Staurosporine; D002118:Calcium