| Project/Area Number |
06454171
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Kansai Medical University |
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Principal Investigator |
ITO Seiji Kansai Medical University, Faculty of Medicine, Professor, 医学部, 教授 (80201325)
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| Co-Investigator(Kenkyū-buntansha) |
SAKAMOTO Kazuichi Osaka Bioscience Institute, 4th Department, Research Scientist, 第4部門, 研究員 (90235169)
SUGATANI Junko Kansai Medical University, Faculty of Medicine, Lecturer, 医学部, 講師 (30098131)
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,100,000 (Direct Cost: ¥7,100,000)
Fiscal Year 1995: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1994: ¥5,100,000 (Direct Cost: ¥5,100,000)
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| Keywords | prostaglandin F_<2alpha> / mouse / gonadotropin / cAMP / progesterone / mRNA / corpus luteum / in situ hybridization / プロスタグランジンF_<2α> / 卵巣 / 黄体機能 / 受容体 / ゴプドトロピン / cAMP / 遺伝子 / PGF合成酵素 / Gq / 黄体 / CHO細胞 |
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| Research Abstract |
It has been recognized for overe two decades that prostaglandin (PG) F_<2alpha> is of prime importance in initiating luteal regression in many species. We succeeded in the cloning of a cDNA encoding PGF_<2alpha> receptor. We recently demonstrated that its mRNA and receptor protein are abundantly expressed in corpus luteum of the ovary throughout the luteal phase of the estrous cycle and early and middle pregnancy, suggesting that PGF_<2alpha> may be involved in not only luteolysis but also luteal functions. This year we focused on the elucidation of the regulatory mechanisms of PGF_<2alpha> receptor mRNA expression and PG production, and obtained following results. 1) We revealed by RNA blot analyzes that serum progesterone level and expression of PGF_<2alpha> receptor mRNA in mouse ovary increased 1-16 h after administration of gonadotropins (PMSG,hCG,FSH) and cholera toxin, which activate adenylate cyclase and increase cAMP level. We also demonstrated that these agents induced the ex
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pression of PGF_<2alpha> receptor mRNA in luteal cells of preexisting mouse ovary. These results supports the above-mentioned notion that PGF_<2alpha> may be involved in not only luteolysis but also luteal funciton. 2) We succeeded in the cloning of PGF_<2alpha> receptor gene and showed that it spans over 30 kb and consists of 3 exons. The promoter region contains several binding motifs for transcription factors and was activated by TPA and forskolin. 3) In order to elucidate the regulatory mechanism of PG production, we first identified three urinary metabolites of PGF_<2alpha> in mice by gas chromatography and mass spectrometry. We examined the change of one of the metabolites and showed that the metabolite increased at the term of pregnancy, suggesting the involvement of PGF_<2alpha> in delivery. 4) We also demonstrated by Western blot analysis with anti-PGF synthase antisera that PGF synthase protein increased at the term of pregnancy and suggested that it may be responsible for the PGF_<2alpha> production. Less
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