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).