| Co-Investigator(Kenkyū-buntansha) |
SAKIHARA Satoru Hirosaki University, University Hospital, Instructor, 医学部附属病院, 助手 (80333722)
KAGEYAMA Kazunori Hirosaki University, School of medicine, Instructor, 医学部, 助手 (30343023)
IWASAKI Yasumasa Kouchi University, School of medicine, Assistant professor, 医学部, 講師 (30303613)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
Physiological regulatory mechanisms of Corticotropin-releasing hormone (CRH), urocortin (Ucn), and its receptors are investigated.
1)In A7r5, aortic smooth muscle cells, it was demonstrated Ucn, one of CRH family peptides, could suppress the CRH receptor type2β (CRFR2β) mRNA expression via CRFR2β itself. Furthermore, it was also demonstrated Ucn or UcnII, the ligands for CRH receptor type2, could augment intracellular IL-6 content through PKC and MAPK, but PKA pathway.
2)It is demonstrated the induction of the feeding suppression and energy expenditure by central administration of neuromedin U is not evident in CRH deficient mice, but wild type mice. These results indicate the central energy-modulative effect of neuromedin U is mediated through CRH.
3)It is demonstrated the anorectic effect following the activation of leptin-melanocortin system is partially diminished in the CRH deficient mice. This indicates CRH is involved in the downstream of melanoeortin system where is critical in the feeding regulation.
4)The synthesis and secretion of POMC-related peptides in anterior pituitary was compared between wild type and CRH deficient mice. The results suggested CRH is involved in the secretion, but not the synthesis and the processing, of ACTH.
5)The RIA system for rat CRH receptor was developed, then, utilized for the quantitative analysis of CRH receptor protein on the surface of rat corticotroph. According to this system, CRH receptor protein was decreased by the adrenalectomy in vivo experiment, and by the treatment with CRH or cAMP in vitro experiment, similar to the fluctuation of its mRNA in the same context.
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