title: Regulation of the expression of corticotropin-releasing factor gene by pyroglutamylated RFamide peptide in rat hypothalamic 4B cells.
abstract: Pyroglutamylated RFamide peptide (QRFP), an important regulator of metabolism and energy homeostasis, has orexigenic effects. QRFP acts via a specific receptor, Gpr103. Gpr103 mRNA is expressed in the rat hypothalamic paraventricular nucleus (PVN). In the PVN, corticotropin-releasing factor (CRF), which plays a central role in regulating the stress response and is produced in response to stress, stimulates the release of adrenocorticotropic hormone from the anterior pituitary. We hypothesized that QRFP regulates CRF gene expression directly in the hypothalamus, and thus examined the direct effect of QRFP on the promoter activity and mRNA levels of CRF in hypothalamic cells. To examine these pathways, we used hypothalamic 4B cells, a homologous PVN neuronal cell line. Gpr103a and Gpr103b mRNA, and Gpr103 (a and b) proteins were expressed in the hypothalamic cells. The Gpr103 mRNA and protein levels were increased by QRFP. QRFP also stimulated CRF mRNA levels and CRF promoter activity directly in 4B cells following their transfection with the CRF promoter. The protein kinase A (PKA) and protein kinase C (PKC) pathways were involved in the QRFP-induced increases in CRF promoter activity. QRFP stimulated cAMP response element-binding protein (CREB) phosphorylation. CREB phosphorylation was inhibited by a PKC inhibitor. PKC-dependent signaling would be upstream of the CREB phosphorylation. Thus, QRFP-dependent pathways are involved in the regulation of CRF gene expression in the hypothalamus.
authors.affiliation: Department of Endocrinology and Metabolism, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ishigame
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kageyama
authors.forename: Shinobu
authors.initials: S
authors.lastname: Takayasu
authors.forename: Kengo
authors.initials: K
authors.lastname: Furumai
authors.forename: Yuki
authors.initials: Y
authors.lastname: Nakada
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
mesh_terms: D000818:Animals; D002460:Cell Line; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011761:Pyrrolidonecarboxylic Acid / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009479:Neuropeptides; C516486:Qrfpr protein, rat; C416987:RFamide peptide; D043562:Receptors, G-Protein-Coupled; D003346:Corticotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid