The effect of stress on adrenocortical DHEA-S secretion

Research Project

Project/Area Number	18K07422
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 52010:General internal medicine-related
Research Institution	University of Human Arts and Sciences
Principal Investigator	Kagitani Fusako 人間総合科学大学, 人間科学部, 教授 (50291133)
Project Period (FY)	2018-04-01 – 2022-03-31
Project Status	Completed (Fiscal Year 2021)
Budget Amount *help	¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000) Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000) Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000) Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords	ストレス / 交感神経 / 副腎皮質 / ステロイドホルモン / DHEA-S / 卵巣 / 性ホルモン
Outline of Final Research Achievements	The present study examined whether increased adrenal sympathetic nerve activity during stress regulates the adrenocortical secretion of dehydroepiandrosterone sulfate (DHEA-S) and pregnenolone, which is synthesized upstream of the DHEA-S synthetic pathway, from the adrenal cortex. In anesthetized adult male rats, the resting DHEA-S concentration in adrenal venous blood was comparable to that in systemic circulating arterial blood. This indicates that, unlike in humans, the rat adrenal cortex does not secrete DHEA-S. During adrenal sympathetic nerve stimulation, the rate of pregnenolone secretion from the adrenal gland was markedly reduced. This suggests that sympathetic nerves are involved in regulating adrenocortical steroid hormone secretion, including DHEA-S.
Academic Significance and Societal Importance of the Research Achievements	DHEAおよびDHEA-Sは，性ホルモン源としてや抗ストレスホルモンとしての働き，高齢者における血中濃度低下が認知症やサルコペニアなどの老年症候群と関連することなどが注目されている．血中DHEA-S値は，コルチゾール同様に視床下部－下垂体前葉系ホルモンによって制御されるが必ずしも血中コルチゾール動態と一致せず，DHEA-S分泌調節機構の解明は未だ十分ではない．本研究は，DHEA-Sを含む副腎皮質ステロイドホルモン合成の律速段階であるプレグネノロン合成・分泌が，副腎支配交感神経により制御される可能性を明らかにした．本成果により，健康寿命の延長に向けての予防策や対応策確立への寄与が期待できる．