title: A 3',5'-cyclic adenosine monophosphate-dependent pathway is responsible for a rapid increase in c-fos messenger ribonucleic acid by adrenocorticotropin.
abstract: ACTH rapidly and transiently increases c-fos mRNA in the rat adrenals in vivo. The present investigation was undertaken in order to determine what kind(s) of second messenger systems is involved in this increase. Rat adrenal cells were grown in monolayers in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum. After 2 days of culture, cells were treated with ACTH and various agents alone or in combination. The amount of c-fos mRNA was determined by dot blot hybridization and corticosterone levels in the media were measured by RIA. ACTH (300 pg/ml) increased c-fos mRNA transiently with a peak level after 60 min. A similar increase was observed when (Bu)2cAMP (1 mM) was substituted for ACTH. Pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide (H-89), a selective inhibitor of cAMP-dependent protein kinase, suppressed both basal and ACTH-increased c-fos mRNA. H-89 also suppressed corticosterone production. On the other hand, neither 12-O-tetradecanoyl-phorbol-13-acetate (100 ng/ml) nor elevated potassium ion (50 mM) affected the amount of c-fos mRNA and corticosterone production. Furthermore, pretreatment with cycloheximide (5 micrograms/ml) increased both basal and ACTH-increased c-fos mRNA. These results indicate that ACTH increases c-fos mRNA by phosphorylation of preexisting trans-acting factor(s) via cAMP-dependent protein kinase in common with steroidogenesis.
authors.affiliation: Department of Endocrinology and Metabolism, Nagoya University, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Miyamoto
authors.forename: H
authors.initials: H
authors.lastname: Seo
authors.forename: K
authors.initials: K
authors.lastname: Kanda
authors.forename: H
authors.initials: H
authors.lastname: Hidaka
authors.forename: N
authors.initials: N
authors.lastname: Matsui
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology*; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D013449:Sulfonamides; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone; D003513:Cycloheximide; D000242:Cyclic AMP; D011494:Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D003345:Corticosterone