Evidence for dual regulation by protein kinases A and C of thyrotropin-releasing hormone receptor mRNA in GH3 cells.
We showed previously that TRH down-regulates TRH receptor (TRH-R) mRNA in GH3 cells by a mechanism that appears to be mediated by protein kinase C. Here we show that vasoactive intestinal peptide (VIP) down-regulates TRH-R mRNA and present evidence that this action is mediated by protein kinase A. In GH3 cells, VIP caused a time- and concentration-dependent decrease in TRH-R mRNA. This VIP effect was simulated by 8-(4-chlorophenylthio)-cAMP, forskolin, cholera toxin and 1-methyl-3-isobutylxanthine. When cells were incubated with agents that elevate cAMP and TRH or phorbol 12-myristate 13-acetate, the decrease in TRH-R mRNA was greater than with either agent alone. When cells were pre-incubated with H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride], an inhibitor of protein kinases, the effects of VIP, TRH and phorbol 12-myristate 13-acetate were inhibited. We suggest that VIP, via protein kinase A, and TRH, via protein kinase C, dually regulate TRH-R mRNA.
Fujimoto
J
J
Department of Medicine, Cornell University Medical College, New York Hospital, NY 10021.
Gershengorn
M C
MC
D000818:Animals; D002460:Cell Line; D000242:Cyclic AMP / Q000502:physiology; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000235:genetics*; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; D014660:Vasoactive Intestinal Peptide; D013973:Thyrotropin-Releasing Hormone; D000242:Cyclic AMP; D011494:Protein Kinases; D011493:Protein Kinase C