Overtraining Syndrome
Physical Exercise

Author: elisabetta fassone
Date: 12/02/2013


Overtraining syndrome has been referred to as '’staleness’’, ’’overreaching’’, and ‘’chronic fatigue’’. It can result in mental lassitude and physical injury and therefore a declining performance. Most simply put, overtraining syndrome is the point at which an athlete exceeds his capacity for exercise. It has both psychological and physiological components that should be recognized by those working with athletes.

Physiological indicators

Effects on Hypothalamo-pituitary-adrenal axis
In an overtrained athlete, an overactive pituitary gland is primarly responsible for physiological responses to overtraining. The main structure of the SNE is the hypothalamus that receives information from various brain areas and the periphery. The hypothalamus, in turn, projects numerous efferents, particularly to the pituitary gland, of which it controls the secretory activity and biological rhythms, and to the limbic areas. These are responsible for behavioral responses induced by stress.
The hypothalamic-pituitary-adrenal axis is the most important structure of the SNE. The SNE responds to stress by increasing the secretion of CFR, epinephrine, serotonin, GABA and glutamic acid. The CRF activates noradrenergic neurons and stimulates the secretion of pituitary ACTH. Stimulation of the hypothalamus causes the pituitary gland to secrete excess adrenocorticotropic hormone. This, in turn, stimulates cortisol secretion by the adrenal cort ex, which aids the body in adapting to stress.

exercise as a stressor to the human neuroendocrine system,2006
neuroendocrine responses to stress
Hypotalamic-pituitary-adrenal axis, neuroendocrin factors and stress,2002

Effects on hypothalamo-pituitary-gonadal axis
The human reproductive system also is adversely affected by overtraining syndrome, with luteinizing hormone (LH) levels decreasing when the athlete is overtrained. In women, LH decrease is associated with decreased percent of body fat and associated decreased levels of estrogen. Stress-associated reproductive disorders are associated with reduced pulsatile secretion of LH and FSH from the pituitary gland, concomitant with decreased expression and release of GnRH from the hypothalamus. The stress-induced rise in glucocorticoids represses GnRH secretion. The hippocampus, a site of abundant GR (glucocorticoid receptor) expression in the brain, mediates a variety of behavioral responses to glucocorticoids and provides indirect inhibitory feedback to the hypothalamus. GR, also present in hypothalamic neurons, directly contribute to glucocorticoid mediated down-regulation of the HPG axis. This conclusion is supported by studies that show GR present in GnRH-containing hypothalamic cell lines functioning as ligand-activated transcriptional regulators. Glucocorticoid treatment in a hypothalamic cell lines repress endogenous GnRH mRNA and the transcriptional activity of transfected GnRH promoter-reporter gene vectors. The element required for glucocorticoid repression of mouse GnRH gene transcription, the distal negative glucocorticoid response element (nGRE), is not bound directly by GR but is recognized by Oct-1. Therefore, one mechanism of glucocorticoid repression of GnRH does not involve direct DNA binding by the GR but rather novel protein-protein interactions between the GR and the DNA-bound Oct-1 transcription factor. In addition to suppressing GnRH synthesis, glucocorticoids decrease the activity of the GnRH pulse-generating center . Together this suggests that the primary site for the inhibitory actions of glucocorticoids on gonadotropin secretion resides at a suprapituitary level, probably through an interruption of hypothalamic GnRH release.
Overtraining in females is often manifested by amenorrhea

glucocorticoids, stress and fertility,2010
effect of stress on the activity of the Hypotalamic-pituitary-gonadal axis: peripherial and central mechanisms,1991

In men, decreased LH results in decreased testosterone and a resultant inability to build muscle mass. Elevated levels of glucocorticoids are also associated with decreased testosterone biosynthesis by Leydig cells. The degree to which glucocorticoids inhibit Leydig cell function is determined by the amount of GR in the cell, the intracellular concentration of glucocorticoids, and the oxidative activity of 11β-hydroxysteroid dehydrogenase (11β-HSD), an enzyme that catalyzes both oxidative and reductive reactions of glucocorticoids. Two 11β-HSD isoforms exist by which Leydig cells regulate their intracellular concentration of glucocorticoid levels, 11β-HSD1 and -2 . The catalytic direction of 11s-HSD1 is determined by the cell type and intracellular milieu. It has been clearly shown that 11β-HSD1 in Leydig cells behaves predominantly as a dehydrogenase, while 11β-HSD1 in liver cells behaves predominantly as a reductase. 11β-HSD2, having no detectable reductase activity, is known to be an exclusively oxidative enzyme. 11s-HSD has therefore been described as a gatekeeper of testicular steroidogenesis in times of stress. Under stressful conditions, the oxidative capacity of 11β-HSD in Leydig cells may be exceeded by high levels of glucocorticoids leading to suppression of testosterone biosynthesis. There is also evidence for a dynamic coupling between 11s-HSD and the enzymes responsible for testosterone biosynthesis. This action would also account for the rapid effects of glucocorticoids on the suppression of testosterone production.
In addition to the rapid effects of glucocorticoids on testosterone production, glucocorticoids have also been reported to induce Leydig cell apoptosis, reducing the number of Leydig cells per testis; they also promote apoptosis of spermatogonia within the seminiferous tubules. It is well known that glucocorticoids induce apoptosis in thymocytes in vitro and in vivo through reductions in the mitochondrial membrane potential and the generation of reactive oxygen species (ROS)

Modification of the immune system
Intense exercise seems to cause a temporary decrease in immune system function. The body, during long, high-intensity activity (marathon, triathlon, swimming, cycling) produces certain hormones that temporarily lower immunity. The circulating numbers and functional capacities of leukocytes may be decreased by repeated intense sports.
Adrenaline and cortisol, the stress hormones, raise blood pressure and cholesterol levels, and depress immune system. This effect have been linked to the increased susceptibility to infection in endurance athletes after extreme exercise. Consequently, excessive exercise is interpreted as a condition of stress by our organism, and the general pattern of hormonal and immunological responses is similar to that of trauma, infection, psychological stress, sepsis, etc.
Nevertheless, falls in concentration of glucose and glutamine can contribute to immunodepression. Also, during exercise, there is an increase production of reactive oxygen species (ROS), and some immune cell functions can be impaired. A raise in gut wall permeability may also allow increased entry of bacterial endotoxins into circulation, particularly during prolonged exercise in the heat. Hence the cause of augmented incidence of infection in people who practice excessive activity is multifactioral, due to a variety of stressors.

During exercise, epinephrine is released from the adrenal medulla, and norepinephrine is released from the sympathetic nerve terminals. Arterial plasma concentrations of epinephrine and norepinephrine increase almost linearly with duration of dynamic exercise and exponentially with intensity. The expression of β-adrenoceptors on T, B, and NK cells, macrophages, and neutrophils in numerous species provide the molecular basis for these cells to be targets for catecholamine signaling . β-Receptors on lymphocytes are linked intracellularly to the adenyl cyclase system for generation of cAMP as a second messenger , and the β-adrenoceptor density appears to change in conjunction with lymphocyte activation and differentiation.
The in vitro effect of epinephrine on NK cell activity has demonstrated that human NK cell activity was inhibited by the addition of cAMP inducers directly to target and effector cells. More complex effects were reported when pretreatment of lymphocytes with low concentrations of epinephrine (10−7 to 10−9 M), followed by removal of the drug, increased NK cell activity . Direct addition of epinephrine (10−6 M) to the lymphocyte-target cell mixture inhibited the NK cell activity.
When epinephrine was present during preincubation of mononuclear cells as well as in the NK cell assay at epinephrine concentrations obtained during exercise, there were no significant in vitro effects of epinephrine on NK cells isolated before, during, or after epinephrine infusion . These results suggest that epinephrine may act by redistributing BMNC subsets within the body, rather than directly influencing the activity of the individual NK cells.
The numbers of adrenergic receptors on the individual lymphocyte subpopulations may determine the degree to which the cells are mobilized in response to catecholamines. In accordance with this hypothesis, it has been shown that different subpopulations of BMNC have different numbers of adrenergic receptors . NK cells contain the highest number of adrenergic receptors, with CD4+ lymphocytes having the lowest number.
Epinephrine may be responsible for the recruitment of NK cells to the blood during physical exercise and other physical stress forms. The experimental basis includes the findings that 1) epinephrine infusion mimics the exercise-induced effect especially on NK and LAK cells, 2) β-adrenergic receptors are upregulated on NK cells during exercise, and 3) β-adrenergic receptor blockade abolishes lymphocytosis during exercise and the increase in NK cell number during head-up tilt. Additional evidence comes from the observation that β2-receptor agonists induce selective detachment of NK cells from endothelial cells. Taken together, the findings strongly support the hypothesis that epinephrine strongly contributes to the recruitment of NK cells from the marginating pool in blood vessels, lymph nodes, spleen, and intestines.

It has been shown that corticosteroids given intravenously to humans cause lymphocytopenia, monocytopenia, eosinopenia, and neutrophilia that reach their maximum 4 h after administration. Exogenous glucocorticosteroid administration, especially in supraphysiological doses, induces cell death of immature T and B cells, whereas mature T cells and activated B cells are relatively resistant to cell death. In agreement, recent work shows that the percentage of proliferative lymphocytes expressing early markers of apoptosis do not increase immediately after or 2 h after intense exercise despite an increase in blood glucocorticoid levels. Incubation of thymocytes and splenocytes with concentrations of corticosterone observed at near-maximal exercise induced profound apoptosis and necrosis after 24 h. Recent studies suggest that exercise-associated induction of apoptosis may contribute to lymphocytopenia and reduced immunity after intense exercise. A study found electrophoretic evidence of DNA damage in circulating lymphocytes after exercise that was accompanied by flow cytometric measures of apoptosis. Another study reported increased intrathymic and intrasplenic membrane lipid peroxides and lower concentrations of intrathymic and intrasplenic superoxide dismutase and catalase antioxidants immediately after a run to exhaustion in rodents. Taken together, these findings indicate reactive oxygen species-mediated lymphocyte damage (apoptosis) that may mediate reduced immunity postexercise.
Infusion of prednisolone caused a redistribution of circulating cells from blood to the bone marrow, decreased cellular localization to lymph nodes, and impaired lymphocyte crossing of high endothelial venules. High doses of corticosteroids inhibit function of NK cells. In vitro studies have shown that pharmacological concentrations of methylprednisolone and hydrocortisone inhibited the NK cell function, partly by an inhibition of the adhesion of effector cells to target cells. Unlike catecholamines, however, cortisol exerts its effect with a time lag of several hours. This suggests that cortisol probably does not have a major role in the acute exercise-induced effects. Moreover, after strenuous exercise, a decrease in glucocorticoid sensitivity by lymphocytes occurs due to downregulation of low-affinity high-capacity type II glucocorticoid receptors on lymphocytes. We hypothesize that cortisol likely has a role in maintaining the neutrophilia and lymphopenia after prolonged, intense exercise such as a marathon. The impact of cortisol on accumulation of memory and naive T lymphocytes and on release/maturation of thymocytes with exercise has not been studied.
It also reduces the expression of cytokines and chemokines from sites of inflammation.

Exercise and the immune system: regulation, integration, and adaptation,2000
immune function in sport and exercise,2007

h3. Psychological indicators

Psychlogical overtraining is characterised by sleep disturbances, prolonged excessive weariness, chronic fatigue and loss of vigor. In addition loss of self confidence, apathy, irritability, depression, anxiety, and confusion also are exhibited. An overtrained athlete may exhibit emotional and motivational imbalance, anger, and hostility, and mood swings are common. Eating disorders and generalized loss of appetite also are observed.

Signs and symptoms

Although manifestation of overtraining syndrome differ from person to person, five main signs and symptoms commonly appear in overtrained athletes.
- An alteration in the circulatory system. Increased morning (resting) heart rate, or more specifically, an increase of more than five beats per minutes is indicative of an overtrained state. Abnormal changes in blood pressure, particularly increased resting blood pressure, also may indicate overtraining.
- Unexplained weight loss. Body composition is altered by training, with the lean body mass increasing and the percentage of body fat decreasing.
- Prolonged,excessive thirst also may be a symptom, for example, increased evening fluin intake. The athlete may exhibit signs of dehydration and may drink copious amounts of fluid after practice.
- Alteration in sleeping patterns
- General psychological malaise

a review of overtraining syndrome- recognising the signs and symptoms,1992

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