Endocrinology, Vol 129, 3430-3432, Copyright © 1991 by Endocrine Society

ARTICLES

Evidence for dual regulation by protein kinases A and C of thyrotropin- releasing hormone receptor mRNA in GH3 cells

J Fujimoto and MC Gershengorn
Department of Medicine, Cornell University Medical College, New York Hospital, NY 10021.

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.