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Stepping Stones along the Exercise Stress Response Pathway

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Two key factors cooperatively regulate the stress response to exercise


Tsukuba, Japan—Athletes and the general population alike train to promote health and physical fitness. With repeated exposure to the minimal stress of exercise, the body adapts. Researchers at the University of Tsukuba have sought to paint a detailed picture of the physiological stress response to moderate-intensity exercise that occurs after the lactate threshold is surpassed. In a recently published study in Neuroendocrinology, the researchers have confirmed that arginine vasopressin and corticotrophin-releasing hormone regulate an important indicator of stress: the adrenocorticotropic hormone.


With sufficiently lengthy moderate-intensity exercise, anaerobic respiration processes contribute to producing fuel for the brain and muscles. Lactic acid can build up in the blood, at which point the stress response kicks in.


The researchers confirmed that, in response to exercise stress in rats, adrenocorticotropic hormone (ACTH) is secreted, which involves the release of arginine vasopressin (AVP) and corticotrophin-releasing hormone (CRH) from hypothalamic neurons into the pituitary portal vessels. They used an established animal exercise-stress model to represent human physiological responses and blockers for each factor. "This avoided the difficulties of earlier studies that had used blood samples only, and were unable to identify the causal relationship between ACTH and AVP and CRH responses during exercise stress," explains Professor Hideaki Soya. Because of the study's design, the research team could evaluate each factor's contribution separately and in combination, as well as factor-related activation in the brain, in response to the exercise protocol.


AVP blockers and CRH blockers had an effect on ACTH release from the anterior pituitary only during running (not before running). Each blocker had an effect alone, yet a larger effect was observed when blockers were administered in combination. Furthermore, both arginine vasopressin and corticotrophin-releasing hormone neurons were activated with exercise stress; however, concentrations of adrenocorticotropic hormone in the blood were only correlated with activation of arginine vasopressin neurons. "Thus, both arginine vasopressin and corticotrophin-releasing hormone may contribute to regulating adrenocorticotropic hormone secretion, in different ways, but may do so cooperatively, and therefore together play an important role in the stress response," says first author Kanako Takahashi.


By uncovering this piece of the puzzle, the precise point at which the stress response is activated by exercise is one step closer to being fully understood. Because excessive stress has profound physiological effects, like delaying recovery from exercise, continued research may provide a clearer picture of the stress response, which could contribute to improved athletic and fitness training efficiency and outcomes.


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This research was supported in part by the Special Funds for Education and Research of the Ministry of Education, Culture, Sports, Science and Technology (MEXT), 1111501004 (H.S.); the Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers of the Japan Society for Promotion of Science (JSPS), HFH27016 (H.S.); KAKENHI Grants-in-Aid for Scientific Research on Innovative Areas, 16H06405 (H.S.); KAKENHI Grants-in-Aid for Scientific Research A, 18H04081 (H.S.) and 21H04858 (H.S.); Japan Science and Technology Agency for Mirai Program, JPMJMI19D5 (H.S.); and a grant from Advanced Research Initiative for Human High Performance (ARIHHP), University of Tsukuba.



Original Paper

The article, "Exercise-induced adrenocorticotropic hormone response is cooperatively regulated by hypothalamic arginine vasopressin and corticotrophin-releasing hormone," was published in Neuroendocrinology at DOI: 10.1159/000521237


Correspondence

Professor SOYA Hideaki
Advanced Research Initiative for Human High Performance (ARIHHP), Faculty of Health and Sport Sciences, University of Tsukuba


Related Link

Faculty of Health and Sport Sciences
Advanced Research Initiative for Human High Performance (ARIHHP)