Differential regulation of corticotropin-releasing factor receptor type 1 (CRF1 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.
Moriyama
Takako
T
The Third Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Aomori 036-8562, Japan.
Kageyama
Kazunori
K
Kasagi
Yoko
Y
Iwasaki
Yasumasa
Y
Nigawara
Takeshi
T
Sakihara
Satoru
S
Suda
Toshihiro
T
D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003609:Dactinomycin / Q000494:pharmacology; D015536:Down-Regulation; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D000099052:CRF Receptor, Type 1
D007093:Imidazoles; D011725:Pyridines; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D003609:Dactinomycin; D000099052:CRF Receptor, Type 1; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C093642:SB 203580