title: Regulation of c-fos, c-jun and jun-B messenger ribonucleic acids by angiotensin-II and corticotropin in ovine and bovine adrenocortical cells.
abstract: Previous work has shown that corticotropin (ACTH) and angiotensin-II (A-II), in addition to their acute steroidogenic effects, exert long-term influences on adrenal cell differentiated function, stimulatory or inhibitory, respectively. Certain nuclear proto-oncogenes have been implicated in the regulation of gene expression in many cell systems. We have investigated the effects of ACTH and A-II on the levels of c-fos, c-jun, and jun-B messenger RNAs (mRNAs), in bovine and ovine (OAC) adrenal fasciculata cells. In both cell types ACTH produced time- (maximum at 1 h) and dose-dependent (ED50 congruent to 10(-12) M) increase in c-fos (2- to 4-fold) and jun-B (10- to 20-fold) mRNA levels but did not affect c-jun. The concentrations required to induce half-maximal mRNA accumulation and cortisol production were similar. A-II also produced a dose-dependent increase in c-fos and jun-B mRNAs but also in c-jun in both cell types, despite the fact that OAC are resistant to the steroidogenic action of the hormone. The stimulatory effects of A-II on c-fos mRNA were higher than those produced by ACTH, whereas the effects on jun-B were similar but ACTH abolished (OAC) or decreased (bovine adrenal fasciculata cells) the stimulatory effects of A-II on c-jun mRNA. The effects of ACTH and A-II on cortisol production and proto-oncogene mRNAs were in part mimicked by 8 Bromo-cAMP and the phorbol ester phorbol-12-myristate-13 acetate plus calcium ionophore A23187, respectively. In the presence of cycloheximide, which blocks the steroidogenic effects of both hormones, proto-oncogene mRNAs were superinduced by both hormones. This result, together with the fact that dexamethasone failed to affect the mRNA levels suggests that the stimulatory effects of ACTH and A-II on proto-oncogene expression were not related to an autocrine/intracrine action of cortisol. Taken together, these findings show that the proto-oncogene mRNAs in normal adrenal cells are regulated by ACTH and A-II, acting through different intracellular pathways. They also demonstrate differential responsiveness of the Jun family to both hormones. Thus, the opposite long-term action of ACTH and A-II on adrenal cell differentiated function could be mediated by its different initial effects on proto-oncogene expression, in particular in the members of the Jun family.
authors.affiliation: Inserm U 307, Hôpital Debrousse, Lyon, France.
authors.forename: I
authors.initials: I
authors.lastname: Viard
authors.forename: S H
authors.initials: SH
authors.lastname: Hall
authors.forename: C
authors.initials: C
authors.lastname: Jaillard
authors.forename: M C
authors.initials: MC
authors.lastname: Berthelon
authors.forename: J M
authors.initials: JM
authors.lastname: Saez
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000302:Adrenal Cortex / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics*; D012756:Sheep; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
chemical_list: D004268:DNA-Binding Proteins; D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D000804:Angiotensin II; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D000324:Adrenocorticotropic Hormone; D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate