Thyrotropin-releasing hormone and c-fos/c-jun genes are colocalized in rat anterior pituitary cells: stimulation of transcription by glucocorticoids.

We recently reported that glucocorticoids (GC) enhance the level of TRH peptide and messenger RNA in anterior pituitary cells. However, the regulating mechanism is as yet unclear. The protooncogenes c-fos/c-jun belong to the class of immediate early genes that are activated in neurons by a variety of stimuli, including GC. Fos protein acts as an intracellular third messenger, regulating gene transcription of neurotransmitters. To determine whether c-fos/c-jun are involved in regulating the effect of GC on TRH in rat anterior pituitary cells, the coexpression and nuclear transcription activity of TRH and c-fos/c-jun after dexamethasone (DEX) stimulation (7 days) were investigated. The double labeled in situ hybridization results demonstrated that TRH and c-fos/c-jun are coexpressed in anterior pituitary cells and that DEX (10(-8) M) enhanced the cell intensity for TRH and c-fos/c-jun. The mean cell intensity of treatment vs. control was 2.4-fold for TRH, 1.4-fold for c-fos, and 1.4-fold for c-jun (n = 24; P < 0.01). The Northern blot analysis also showed that DEX increased the messenger RNA level of TRH 5.1-fold (n = 4; P < 0.01), that of c-fos 1.8-fold (n = 5; P < 0.01), and that of c-jun 4.2-fold (n = 4; P < 0.01). The nuclear run-on analysis indicated that DEX increased the nuclear transcription activity of TRH 3.3-fold, that of c-jun 3.2-fold, and that of c-fos 3-fold (n = 3; P < 0.01) vs. the control value. The coexpression of TRH and c-fos/c-jun in anterior pituitary cells as well as the enhancement of transcription after DEX treatment raise the possibility that c-fos/c-jun could mediate the effect of GC on TRH gene transcriptional activity.