Differential regulation of corticotropin-releasing factor receptor type 1 (CRF 1 receptor) mRNA via protein kinase A and mitogen-activated protein kinase pathways in rat anterior pituitary cells

Corticotropin-releasing factor (CRF) receptor type 1 (CRF 1 receptor) mRNA levels are down-regulated by CRF via the cyclic AMP-protein kinase A (PKA) pathway. In this study, we focused on the involvement of both the mitogen-activated protein (MAP) kinase pathway and PKA in this regulation. Real-time PCR (RT-PCR) revealed that a MAP kinase, extracellular signal-regulated kinases 1/2, pathway was also involved in the down-regulation of CRF 1 receptor mRNA levels by CRF in the rat anterior pituitary (AP). Down-regulation of CRF 1 receptor mRNA levels was caused by a post-transcriptional system such as mRNA degradation, as incubation with CRF significantly decreased the half-life of CRF 1 receptor mRNA. Furthermore, pre-treatment with a PKA inhibitor completely blocked CRF-induced CRF 1 receptor mRNA destabilization, while pre-treatment with an extracellular signal-regulated kinases 1/2 inhibitor had no inhibitory effect. These results suggested that in the rat AP, down-regulation of CRF 1 receptor mRNA levels is caused by mRNA degradation via PKA, but not by the MAP kinase pathway.