Analysis of age-associated change of glucocorticoid production

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K08286
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Teikyo University
• Principal Investigator: Adachi Mimi 帝京大学, 医学部, 教授 (10323693)
• Co-Investigator(Kenkyū-buntansha): 岡崎 具樹 帝京大学, 医学部, 教授 (60203973)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 老化 / 糖質コルチコイド / GADD45A / p38MAPK / HPA軸

Outline of Final Research Achievements

Glucocorticoid production is regulated by adrenocorticotropic hormone (ACTH) via the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) pathway in the adrenal cortex, but the changes in steroidogenesis associated with aging are unknown. (1)We reported that in human adrenocortical tumor cell line, H295R cells, which were induced to replicative or drug-induced senescence, glucocorticoid production and most of steroidogenic factors gene expression were increased. Further those are promoted through GADD45A and p38MAPK, but not through ACTH/PKA pathway.(2)We found that the amount of glucocorticoid in serum is higher in old mice, and that circadian rhythm is disappeared.
These results suggest that glucocorticoid production is changed associated with aging. It is possibility that deregulation of glucocorticoid production might play a key role in progression of aging and age-associated diseases.

Free Research Field

分子生物学、生化学、内科学、循環器内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、老化に伴い出現する新規の糖質コルチコイド分泌活性化メカニズムが発見され、その老化への関与が示唆された。したがって、糖質コルチコイド分泌脱制御が、炎症・活性酸素・ミトコンドリアの機能・小胞体ストレスに次ぐ、老化の原因の新たな役者として治療戦略のターゲットになることが期待される。加齢により罹患率が上昇する老化関連疾患すなわち、動脈硬化、耐糖能異常、脂質代謝異常症、免疫能低下、骨粗鬆症など、多くの疾患がそのターゲットになり得ることが期待されるため、広く成人疾患の治療戦略として波及することが期待され、学術的、社会的な意義は大変大きいと思われる。