Enhancement of hypothalamic-pituitary activity in male athletes: evidence of a novel hormonal mechanism of physical conditioning

BMC Endocr Disord. 2019 Nov 1;19(1):117. doi: 10.1186/s12902-019-0443-7.


Background: Exercise is known to induce multiple beneficial conditioning processes. Conversely, although exercise may generate several hormonal effects, an intrinsic hormonal conditioning process has not been reported. In the Endocrine and Metabolic Responses on Overtraining Syndrome (EROS) study, we observed inherent and independent conditioning processes of the hypothalamic-pituitary axes in athletes. Our objective is to describe the theory of the novel hormonal conditioning mechanism using the findings from the EROS study.

Methods: In this cross-sectional study, we selected 25 healthy athletes (ATL) and 12 non-physically active healthy controls (NPAC), 18-50 years old, males, with BMI 20-30 kg/m2, with similar baseline characteristics, who underwent gold-standard exercise-independent tests: cosyntropin stimulation test (CST) and insulin tolerance test (ITT), to evaluate cortisol response to CST, and ACTH, cortisol, GH, and prolactin responses to an ITT.

Results: Responses to ITT were significantly earlier and higher in ATL than NPAC for cortisol [Mean ± SD: 21.7 ± 3.1 vs 16.9 ± 4.1 μg/dL; p < 0.001], GH [Median (95% CI): 12.73 (1.1-38.1) vs 4.80 (0.33-27.36) μg/L; p = 0.015], and prolactin [24.3 (10.5-67.45) vs 10.50 (6.21-43.44) ng/mL; p = 0.002]. Cortisol response to CST was similar between ATL and NPAC. During ITT, cortisol, GH, and ACTH mean increase in ATL were 52.2, 265.2, and 18.6% higher than NPAC, respectively. Prolactin response was absent in NPAC, while present in ATL.

Conclusions: We found sufficient evidence to propose the existence of a diffuse enhancement of the hypothalamic-pituitary activity in athletes, not restricted to any axis, showing an intrinsic and independent process of "hormonal conditioning" in athletes, similar to those observed in the cardiovascular and neuromuscular systems. This novel conditioning process may be the missing link for understanding the improved responses observed in athletes to harmful situations, traumas, infections, inflammations, and psychiatric conditions.

Keywords: Anterior pituitary; Hormonal conditioning; Hypothalamus; Sports endocrinology.

MeSH terms

  • Adolescent
  • Adult
  • Athletes / statistics & numerical data*
  • Cosyntropin / administration & dosage*
  • Cross-Sectional Studies
  • Exercise Test
  • Exercise*
  • Female
  • Hormones / administration & dosage
  • Humans
  • Hydrocortisone / metabolism*
  • Hypoglycemic Agents / administration & dosage
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism*
  • Insulin / administration & dosage*
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism*
  • Prolactin / metabolism
  • Young Adult


  • Hormones
  • Hypoglycemic Agents
  • Insulin
  • Cosyntropin
  • Prolactin
  • Hydrocortisone