Regulation of vasopressin messenger RNA levels in the small cell lung carcinoma cell line GLC-8: interactions between glucocorticoids and second messengers.
The role of glucocorticoids and second messenger systems in the regulation of the vasopressin (VP) gene was studied in the human small cell lung carcinoma cell line GLC-8. Small cell lung carcinoma GLC-8 cells express VP mRNA and contain both glucocorticoid and mineralocorticoid receptors. Treatment with the synthetic glucocorticoid dexamethasone when added alone at 10(-8) M had no effect on the VP mRNA level and decreased the level by 30% at 10(-6) M. However, the effect of dexamethasone changed to positive when cells were simultaneously treated with cAMP-enhancing agents. VP mRNA levels, which were elevated by 1.5- to 2-fold by the cAMP-enhancing agents alone, increased a further 1.5- to 3-fold by dexamethasone. Thus, the combined effect of dexamethasone and cAMP stimulation was a 3- to 7.5-fold increase in VP mRNA levels. Long term treatment with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) reduced the VP mRNA level by 75%. The TPA-suppressed VP mRNA levels could be up-regulated about 6-fold by simultaneous treatment with 8-bromo-cAMP. Dexamethasone did not alter the TPA-suppressed VP mRNA levels. These results indicate that both cAMP and protein kinase-C pathways as well as glucocorticoid receptors are involved in the regulation of VP mRNA levels and that these factors interact. This leads to a negative or positive response of VP gene expression to glucocorticoids in a state-dependent manner. The interactions may be of significance in a physiological context and relate to the different regulation of VP-expressing systems in the brain.
Verbeeck
M A
MA
Rudolf Magnus Institute, Department of Pharmacology Medical Faculty, University of Utrecht, The Netherlands.
Sutanto
W
W
Burbach
J P
JP
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology*; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics*; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology*; D003907:Dexamethasone / Q000378:metabolism / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*; D015290:Second Messenger Systems / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014667:Vasopressins / Q000235:genetics*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014667:Vasopressins; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000450:Aldosterone; D003907:Dexamethasone; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine; D006854:Hydrocortisone