Transcriptional regulation by dexamethasone of endogenous thyrotropin-releasing hormone receptor messenger ribonucleic acid in rat pituitary GH4C1 cells

Previous molecular studies on the mechanism of regulation of TRH receptor (TRHR) mRNA used transfected cells and concluded that the major mode of regulation is via mRNA degradation. Glucocorticoid hormones induce an increase in the number of TRHRs in rat pituitary GH cells, the model system used most extensively to characterize these receptors. We prepared a probe from the recently cloned rat lactotroph TRHR cDNA and investigated the mechanism of regulation by dexamethasone of endogenous TRHR mRNA in GH4C1 cells. Incubation with dexamethasone (100 nM for 6-48 h) induced a 3-to 4-fold increase in the steady state TRHR mRNA concentration (maximum at 24 h), as determined by Northern blot analysis. The stimulation was specific for glucocorticoids and dose dependent over the range 1-500 nM (maximum effect reached at 10 nM). The rate of transcription of the TRHR gene, measured by a nuclear run-on assay, was increased 3.0 +/- 0.57-fold (mean +/- SE) in cells treated for 12 h with 100 nM dexamethasone. We conclud...