The classical negative feedback loop for cortisol secretion is associated with inhibition and production of CRH and ACTH to suppress cortisol release and concentration.
On one hand, high salivary cortisol concentrations since the beginning of the day may be associated with female gene, specifically the production of cortisol intensified by estrogen in the hypothalamus-pituitary-adrenal axis, a higher mean value of cortisol, and a greater predisposition to its absorption15.
On the other hand, the high salivary cortisol concentration found may also be associated with a suppression of glucocorticoid receptors (GR, glucocorticoid receptor – NR3C1). This fact is related to the effect of adaptation to training and to a protective effect regarding overtraining16, 17.
GRs are a family of receptors consisting of three main domains. The first one is the N-terminal domain (NTD), responsible for transcriptional activation function (AF1), which interacts with co-regulators, representing the main site for post-translational modifications (PTMs). The second one is the DNA-binding domain (DBD), which is the most preserved domain in the entire receptor. It has two zinc finger regions, which recognize and associate with the target DNA sequence, called glucocorticoid-responsive elements (GRE), and it is responsible for the transcriptional activation function (AF1) in association with co-regulators. The last one is the C-terminal region of the ligand-binding domain (LBD), comprising 12 beta propellers and four beta sheets. It constitutes a hydrophobic region for the ligand substance (e.g. cortisol) and contains an activation function (AF2) that depends on cortisol to interact with co-regulators18, 19, 20.
Barrientos et al.21 demonstrated a decrease in the levels of expression of GR in the hippocampus in elderly animals submitted to exercises. These findings corroborate previous studies and suggest that prolonged basal increases in cortisol levels in the hippocampus are associated with potential inflammatory responses, as recently demonstrated by other authors22, 23. This seems to support the idea that a decreased expression of GR may be associated with a protective effect.
Previous findings have indicated that high cortisol levels increase insulin resistance and metabolic syndrome. Paradoxically, evidence indicates that aerobic exercises attenuate the development of metabolic syndrome, although they stimulate acute increases in circulating cortisol levels24, 25.
This action seems to be associated with the lipolytic nature of cortisol. The literature has shown that increased glucocorticoids in insulin-sensitive tissues is related to lipid accumulation and metabolic complications, independently of plasma concentrations. The action of intracellular cortisol is determined by both 11beta-hydroxysteroid dehydrogenase type 1 (11-βHSD1) and GR. Research studies have proved that training can increase the concentration of 11βHSD1 as well as GR in the adipose tissue, resulting in increased lipolysis26, 27.
Another important aspect to be considered is the so-called anticipatory salivary cortisol response before competition, which is well described in the literature. It does not depend on the type and nature of the sport, not even on the existence or not of an opponent and/or physical contact28. The anticipatory salivary cortisol response has been strongly related to precompetitive anxiety29,30.
Cevada et al. 31 reviewed the literature and showed that most studies have evaluated male athletes, while three have evaluated female athletes, and one study have included both genders. Among these studies, only those involving women showed statistically significant differences, showing that female athletes seem to be more vulnerable to physical stress than men.32
Changes in both cortisol and testosterone concentrations have been associated with motivational factors and aggression; in this context, a positive correlation between dominance and fighting status is a central aspect of this change31. These aspects have been well described in a recent meta-analysis that compared the effects of this association on individuals of both genders, demonstrating a clear increase in cortisol levels in women, which was associated with competitive events (e.g. games and fights).