Regulation of primary response and specific genes in adrenal cells by peptide 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 factors 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 mRNA levels of genes expressed in BAC coding for ACTH and AT1 receptors, cytochrome P450scc and P450 17 alpha and 3 beta-hydroxysteroid dehydrogenase (3 beta-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 (cfos, c-jun, and jun-B), decreased 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 effects 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 species-specific differences are related to a different effect of these factors on proto-oncogene expression is not yet known.
Penhoat
A
A
INSERM-INRA U418, Hôpital Debrousse, Lyon, France.
Ouali
R
R
Viard
I
I
Langlois
D
D
Saez
J M
JM
D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D002478:Cells, Cultured; D004351:Drug Resistance; D015972:Gene Expression Regulation, Neoplastic; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011945:Receptors, Angiotensin / Q000187:drug effects; D018043:Receptors, Corticotropin / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D015383:Zona Fasciculata / Q000166:cytology / Q000187:drug effects; D015385:Zona Reticularis / Q000166:cytology / Q000187:drug effects
D006133:Growth Substances; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D018043:Receptors, Corticotropin; D016212:Transforming Growth Factor beta; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone