Elevated basal adrenocorticotropin and evidence for increased central opioid tone in highly trained male athletes

Basal cortisol and ACTH levels have previously been shown to be elevated in highly trained athletes, whereas the ACTH response to ovine CRH has been reported to be diminished compared to that in nonathletic controls. Naloxone, a nonselective opioid receptor antagonist, is known to stimulate ACTH and cortisol secretion. The mechanism of this response is thought to be via increased hypothalamic CRH secretion. The aim of this study was to examine basal and naloxone-stimulated levels of hypothalamic-pituitary-adrenal axis hormones in male athletes. Ten highly trained male athletes and 10 nonathletic controls took part in the study. Peripheral venous blood was sampled for cortisol, ACTH, CRH, and arginine vasopressin (AVP) for 2 h before the administration of 20 mg naloxone, i.v., and 15, 30, 45, 60, 90, and 120 min after naloxone treatment. Body mass index was significantly lower in the athletes (P < 0.001). Basal (prenaloxone) ACTH levels were higher in the athletes (P < 0.05), whereas levels of cortisol, CRH, and AVP were similar in both groups. After naloxone treatment, there was a significantly greater rise in ACTH in the athletes (P < 0.02). There was also a trend for the cortisol response to be greater, which was not statistically significant (P < 0.07). Although in both groups, peripheral CRH rose after naloxone treatment (P < 0.005), a rise of similar magnitude occurred over the 2-h period before naloxone (P < 0.0001). Plasma AVP did not change significantly after naloxone treatment. Neither the plasma cortisol level at baseline nor the body mass index correlated significantly with the ACTH or cortisol response to naloxone. The presence of an enhanced ACTH response to naloxone is evidence that central opioid tone may be increased in highly trained athletes. However, there is no associated suppression of the hypothalamic-pituitary-adrenal axis, and basal ACTH levels are raised, without any detectable change in peripheral plasma CRH or AVP. An additional factor (other than CRH) that stimulates ACTH secretion may be released after naloxone administration.