2013 Fiscal Year Final Research Report
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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| Keywords | 低栄養 / ストレス / 下垂体 / microRNA / HPA軸 |
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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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