2004 Fiscal Year Final Research Report Summary
Physiological role of CRH type 2 receptor and its endogenous ligands
| Project/Area Number |
15590980
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Kochi University |
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Principal Investigator |
HASHIMOTO Kozo Kochi Unversity, Kochi Medical School, Professor, 医学部, 教授 (60033370)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIOKA Tatsuya Kochi Unversity, Kochi Medical School, Lecturer, 医学部附属病院, 講師 (40253356)
ASABA Koichi Kochi Unversity, Kochi Medical School, Assistant, 医学部, 助手 (00314998)
TANAKA Yasushi Kochi Unversity, Kochi Medical School, Assistant, 医学部附属病院, 助手 (80380319)
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| Project Period (FY) |
2003 – 2004
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| Keywords | CRH(CRF) / Urocortin 2(Ucn-2) / Urocortin 3(Ucn-3) / CRH type 2 receptor(CRHR2) / ACTH / corticosterone / AVP |
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| Research Abstract |
1.Effect of stress on the expression of Urocortin 2(Ucn-2) in the brain
Rats subjected to immobilization exhibited a dramatic induction of Ucn 2 mRNA expression in the parvocellular part of the PVN at the end of 2hr immobilization. In contrast, water deprivation for 3 days induced Ucn-2 mRNA expression mainly in the magnocellular part of the PVN. Double-label in situ hybridization revealed colocalization of Ucn 2mRNA in approximately 45% of the CRH mRNA-expressing cells in the paravocellular part of the PVN following immobilization, or colocalization in most of the vasopressin mRNA-expressing mRNA-expressing cells in the magnocellular part of the PVN following water deprivation.
2.Effect of intraventricular (icv) administration of Ucn-2 and Ucn-3 on hypothalamic CRH and AVP expression and plasma ACTH. AVP and corticosterone secretion
1)Effect of icv Ucn-2
Icv administration of Ucn-2 (7.5μg) caused an elevation of plasma ACTH at 5-15 min. It increased the expression of CRH heteronuclear (hn
… More
) RNA and c-fos mRNA at 15 min and at 15-30 min after the administration, respectively, in the hypothalamic paraventricular nucleus(PVN). The expression of AVP hnRNAin the magnocellular part of PVN and supraoptic nucleus (SON) did not change after icv Ucn-2.
2)Effect of Ucn-3
Icv administration of Ucn-3 (7.5μg) stimulated plasma ACTH and corticosterone secretion at 5-30 min and at 15-30 min after the administration, respectively. It also stimulated CRH hnRNA and c-fos mRNA expression at 15 min and at 15-30 min after the administration, respectively, in the hypothalamic PVN. Icv Ucn-3 caused plasma AVP elevation at 5 min. However, the expression of AVP hnRNA in the magnocellular part of PVN and supraoptic nucleus (SON) did not change after icv Ucn-3 administration.
3)Effect of icv administration of nonspecific CRH receptor antagonist α-helical CRF 9-41(αhC) and specific CRHR2 antagonist antigauvagine-30(ASV-30) on Ucn-2-induced ACTH secretion.
Icv administration of αhC or ASV-30 inhibited Ucn-2-and Ucn-3-induced plasma ACTH secretion.
3.Conclusion
These results suggest that Ucn-2 stimulates CRH-ACTH secretion via CRHR2 and that Ucn-2 and Ucn-3 maybe involved at least in part in stress-induced ACTH secretion. Less
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