| Project/Area Number |
20591916
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Shimane University |
|---|
Principal Investigator |
MIYAZAKI Kohji Shimane University, 医学部, 教授 (50145322)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KANASAKI Haruhiko 島根大学, 医学部, 講師 (10325053)
ORIDE Aki 島根大学, 医学部, 助教 (00423278)
|
|---|
| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
|---|
| Keywords | ゴナドトロピン / 下垂体 / GnRH / ERK / MKP / PACAP |
|---|
| Research Abstract |
In this present study, we examined the expression of MKP-1 by GnRH stimulation and investigated the possible role of MKP-1 on gonadotropin gene expression using gonadotroph cell line, LβT2 cells. MKP-1 expression was remarkably increased 60minutes after GnRH stimulation and ERK activation was gradually decreased after 60minutes. GnRH-induced ERK activation was completely inhibited in the presence of U0126, a MEK inhibitor, whereas GnRH-induced MKP-1 expression was partially inhibited by U0126. GnRH-induced MKP-1 induction was inhibited by dose dependently in the presence of triptolide, a diterpenoid triepoxide. On the other hand, ERK activation was potentiated at this time by this compound. U0126 prevented GnRH-stimulated gonadotropin LHβ and FSHβ subunit promoter activity by dose dependently. Whereas, GnRH-stimulated LHb and FSHb promoter activities were almost completely inhibited by triptolide. In addition, under pulsatile GnRH stimulation, MKP-1 expression was observed in high frequency GnRH pulse which preferentially increase LHb, but not in low frequency pulse under which FSHb preferentially increased. Our study demonstrated that MKP-1 induced by GnRH works not only as an ERK-inactivating phosphatase, but also as an important mediator which control gonadotoropin subunit gene expressions.
|
