Importance of Thyrotropin-releasing hormone of hypothalamic paraventricular nucleus for the hypothalamic-pituitary-thyroid axis and the leptin-induced thyroid hormone regulation in mice

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09872
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Gunma University
• Principal Investigator: SHIBUSAWA NOBUYUKI 群馬大学, 医学部附属病院, 非常勤講師 (90396622)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 内分泌代謝 / 視床下部 / 甲状腺

Outline of Final Research Achievements

Thyrotropin-releasing hormone (TRH) in the hypothalamic paraventricular nucleus has been reported to be crucial for the hypothalamic (TRH)-pituitary (TSH)-thyroid axis and the leptin-induced stimulation of blood thyroid hormone in mice. However, TRH is known to be distributed not only hypothalamic paraventricular nucleus but also whole hypothalamus as well as whole brain and body. To gain further insight into significance of paraventricular nucleus (PVN) we established paraventricular specific TRH knock out mice by mating floxed TRH gene mice and Sim1-Cre mice showing deletion of preproTRH gene in paraventricular region. These Sim1-Cre;TRHflox/flox mice showed tertiary hypothyroidism just like null TRH deficient mice, showing mild hypothyroidism with slightly elevated serum TSH levels.　These findings further support evidence of TRH in PVN was crucial for H-P-T axis.

Free Research Field

内分泌学

Academic Significance and Societal Importance of the Research Achievements

TRHは視床下部ホルモンとして主にH-P-T axisのフィードバック機構と、さらにいくつかの神経ネットワークによって分泌調整され、甲状腺ホルモン分泌を介して絶食や環境変化に対するエネルギー消費を調節し代謝のホメオスターシスに重要な役割を持つと考えられる。生体内に広く存在するTRHの機能や役割はまだ全ては解明されていない。今回のモデルマウス解析によりこれまで言及されてきた作用を検証できると考える。さらに肥満、糖尿病、摂食障害などの疾患の克服は現代社会において重要な課題の一つといえる。本研究により得られるTRH作用の証明は、これら疾患の発症病理の解明や治療のヒントを得ることに繋がると期待される。