Pituitary miR-449a modulates CRF type 1 receptor expression and thereby mediates hypothalamic-pituitary-adrenal axis abnormality in offspring from malnourished rat dams
| Project/Area Number |
23791238
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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 |
Embryonic/Neonatal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 低栄養 / ストレス / 下垂体 / microRNA / HPA軸 / 出生時低体重児 / 短体長低体重 / CRF1型受容体 / グルココルチコイド / 低出生体重児 / 低栄養妊娠 / ストレス応答 / 低出生体重 / マイクロRNA |
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| Research Abstract |
Low birth weight is related to increase incidence of psychopathologies later in life. Recent studies suggest that maternal malnutrition affects fetal programming of hypothalamic-pituitary-adrenal (HPA) axis although the mechanism is unknown. We demonstrated that low birth weight offspring (LBW) delivered from malnourished dams showed prolonged HPA axis activation compared with that of control offspring (NBW) and impaired downregulation of corticotropin-releasing hormone (CRH) receptor type 1 (CRHR1) in the anterior pituitary (AP) in immobilization. Immobilization increased expression of AP miR-449a, which has a sequences predicted to bind to the CRHR1 3'UTR in NBW, but not in LBW. Overexpression of miR-449a decreased CRHR1 expression and CRHR1 3'UTR activity in vitro. These results indicated that impairment of miR-449a expression causes the dysregulation of AP CRHR1 expression, resulting in prolonged HPA axis activation in stress in LBW.
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Report
(4 results)
Research Products
(15 results)
