Hypothalamic hypogonadism: Elucidation of the mechanisms controlling GnRH neural activity via Toll-like receptor 4
| Project/Area Number |
16K20218
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | St. Marianna University School of Medicine |
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Principal Investigator |
Fujioka Hitomi 聖マリアンナ医科大学, 医学部, 講師 (50410064)
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| Research Collaborator |
AKEMA Tatsuo
FUNABASHI Toshiya
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | GnRH / macrophage / LPS / LH / ストレス / 機能性視床下部性性腺機能低下 / 視床下部性性腺機能低下 / 神経内分泌 / 生植生理学 |
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| Outline of Final Research Achievements |
Inflammatory/immune challenge is known to suppress LH secretion. We previously discovered that the pretreatment with minocycline (Mino), a potent inhibitor of microglia activation, significantly alleviate the suppression of ovarian steroid-induced LH surge by lipopolysaccharide (LPS) in ovariectomized rats. We also found that Mino suppressed LPS induced interleukin 1β (IL-1β) expression in macrophage in the OVLT. In the present study, we examined distribution of IL-1 receptor in the preoptic area/OVLT, and found IL-1 receptor mRNA located in some vascular structure but not GnRH neurons. Next, we examined whether kiss1 neurons were involved in suppression of LH surge by LPS. We found LPS treatment decreased c-Fos expression in both the kiss1 and GnRH neurons at the peak time of LH surge, that was ameliorated by Mino pretreatment. These results suggest IL-1β induced by LPS suppress GnRH neural activity indirectly through depression of activity in the kiss-1 neurons.
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| Academic Significance and Societal Importance of the Research Achievements |
機能的な視床下部性性腺機能低下はストレスと関連があることが知られている。本研究は、感染ストレスをモデルとして、脳内の免疫担当細胞を介したLHサージ状分泌抑制メカニズムの解明を目指し、その一端を明らかにした。近年、ストレスにより、脳内の免疫担当細胞の活性化が示されていることから、今回の研究の結果は、感染ストレスモデルを超えて、ストレスによる機能的な視床下部性性腺機能低下にも、共通するメカニズムである可能性が考えられる。
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Report
(4 results)
Research Products
(4 results)
