2010 Fiscal Year Final Research Report
The role of reactive oxygen species as bioactive substances in the regulation of luteal function
| Project/Area Number |
20591918
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
SUGINO Norihiro Yamaguchi University, 大学院・医学系研究科, 教授 (10263782)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAMURA Hiroshi 山口大学, 医学部付属病院, 准教授 (50379947)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Keywords | 生殖医学 |
|---|
| Research Abstract |
This study was undertaken to investigate how prostaglandin F2α(PGF2α) increases PGF2αsynthesis and cyclooxygenase-2 (COX-2) expression in the corpus luteum in pseudopregnant rats. We further investigated the molecular mechanism by which PGF2αstimulates COX-2 expression. PGF2α (3 mg/kg) or phosphate buffer as a control was injected subcutaneously on day 7 of pseudopregnancy. COX-2 mRNA expression and PGF2αconcentrations in the corpus luteum were measured 2 h, 6 h, and 24 h after PGF2αinjection. PGF2αsignificantly increased COX-2 mRNA expression at 2 h and luteal PGF2αconcentrations at 24 h. PGF2αsignificantly decreased serum progesterone levels at all of the times studied. Simultaneous administration of a selective COX-2 inhibitor (NS-398, 10 mg/kg) completely abolished the increase in luteal PGF2αconcentrations induced by PGF2α. PGF2αincreased NF-κB p65 protein expression in the nucleus of luteal cells 30 min after PGF2αinjection, and electrophoretic mobility shift assay revealed that PGF2αincreased binding activities of NF-κB to the NF-κB consensus sequence of the COX-2 gene promoter. Simultaneous administration of both superoxide dismutase (SOD) and catalase to scavenge reactive oxygen species (ROS) inhibited the increases of nuclear NF-κB p65 protein expression, lipid peroxide levels, and COX-2 mRNA expression induced by PGF2α. In conclusion, PGF2αstimulates COX-2 mRNA expression and PGF2αsynthesis through NF-κB activation via ROS in the corpus luteum of pseudopregnant rats.
|
