Adaptation of the hypothalamopituitary adrenal axis to chronic exercise stress in humans

Repeated acute or chronic exposure to a particular stress results in adaptation whereby the hypothalamopituitary adrenal (HPS) axis becomes less responsive to subsequent or continued exposure to that particular stress. To investigate the adaptive changes that occur in the HPA axis in response to chronic stress in humans, we studied the effect of chronic exercise stress on basal activity of the HPA axis in six highly trained male ultramarathon athletes and six healthy male controls matched for body mass index. After 3-5 of abstention from intense physical activity, the subjects were admitted to a metabolic study ward at 1600 h. Peripheral blood was sampled initially at 0300 h, at 20-min intervals from 0400 to 0900 h, hourly from 0900 to 1200 h, and then every 2 h from 1200 to 1600 h. A 24-h urine collection was completed during the admission. Peripheral blood adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. Plasma and urinary cortisol were measured by enzyme-linked immunoassay. Plasma and injury cortisol were measured by enzyme-linked immunosorbent assay (ELISA). Plasma ACTH and cortisol levels showed the expected diurnal change in athletes and control subjects (P = 0.00001). However, the early morning ACTH and cortisol surge occurred earlier in the athletes than in the controls (P = 0.026). Plasma ACTH levels were significantly higher in the athletes than in the control subjects (P = 0.0026). There was, however, no significant overall difference in plasma cortisol levels between the athletes and the control subjects, and urinary excretion of free cortisol was similar in the two groups. These data show that intense physical training leads to adaptive changes in basal HPA function, including a phase shift and increased pituitary in basal HPA function, including a phase shift and increased pituitary ACTH secretion, but also blunting of the adrenal cortisol response.