Non-genomic mechanisms of glucocorticoid inhibition of adrenocorticotropin secretion: possible involvement of GTP-binding protein.
We investigated non-genomic mechanisms of glucocorticoid negative feedback regulation on pituitary corticotroph cells using the AtT20 mouse corticotroph tumor cell line. A synthetic glucocorticoid dexamethasone (100 nM) potently suppressed forskolin-induced cAMP generation, adrenocorticotropin (ACTH) secretion, and proopiomelanocortin gene expression. When de novo gene expression was inhibited by actinomycin D (1 microM), dexamethasone still suppressed cAMP efflux and ACTH release, although less potently. Interestingly, under the same conditions, pretreatment of the cells with pertussis toxin (50 ng/ml) completely abolished the suppressive effect of dexamethasone on both parameters. These results suggest that non-genomic and genomic mechanisms are involved in the glucocorticoid negative regulation of ACTH expression, and a pertussis toxin-sensitive GTP-binding protein might, at least partly, participate in the non-genomic effect.
Iwasaki
Y
Y
First Department of Internal Medicine, Nagoya University School of Medicine, Showa-ku, Japan. iwasakiy@mb.in-foweb.or.jp
Aoki
Y
Y
Katahira
M
M
Oiso
Y
Y
Saito
H
H
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000324:Adrenocorticotropic Hormone / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D037342:Pertussis Toxin; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D005938:Glucocorticoids; D011500:Protein Synthesis Inhibitors; D010566:Virulence Factors, Bordetella; D003609:Dactinomycin; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins