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Burnout constitutes a serious health concern in the modern working environment. It is a stress-related condition that has developed as a result of a prolonged psychosocial stress exposure causing a persistent mismatch between demands and resources. The main symptom is emotional exhaustion, but physical fatigue, diminished professional efficacy, cynicism, and cognitive impairments are also associated with this condition. Burnout has been used both as a psychologic term in occupational settings and as a clinical diagnosis in patient populations, and there is currently no universally accepted definition and diagnostic criteria of burnout. It has been hypothesized that the two main stress response systems, the autonomic nervous system (ANS) and the hypothalamus-pituitary-adrenal axis (HPA axis), are involved in the pathogenesis of burnout. A common hypothesis is that in the early stages of chronic stress, the HPA axis and sympathetic ANS activity tend to be higher, while it will decrease with a longer duration of chronic stress to ultimately reach a state of hypoactivity in clinical burnout. The current research in this field shows many contradictory results. Thus there is no compelling evidence of either ANS or HPA dysfunction in burnout. However, there is partial support for the hypothesis of HPA and sympathetic hyperactivity in early stages, and HPA hyporeactivity and low vagal activity in more severe burnout cases, but high-quality studies investigating the causal links are still lacking.

The hypothalamus, lying on the central part of the brain, represents an intersection for many nervous pathways. Through the sensory inputs the hypothalamus detects changes in the internal and external environments. All these data put the hypothalamus in a key position to control many bodily functions using three major outputs: the autonomic, endocrine, and behavioural systems. The autonomic control contains hypothalamic neurons projected to the preganglionic neurons of the autonomic system, sympathetic and parasympathetic. The hypothalamo-hypophyseal axis allows the control of the endocrine system. In the relationship with the limbic system, the hypothalamus is involved in emotion control.

Context The 250-μg short Synacthen (corticotropin) test (SST) is the most commonly used tool to assess hypothalamo-pituitary-adrenal (HPA) axis function. There are many potentially reversible causes of adrenal insufficiency (AI), but no data to guide clinicians as to the frequency of repeat testing or likelihood of HPA axis recovery. Objective To use the SST results to predict adrenal recovery. Design A retrospective analysis of 1912 SSTs data. Patients Seven hundred seventy-six patients with reversible causes of AI were identified who had at least two SSTs performed. A subgroup analysis was performed on individuals previously treated with suppressive doses of glucocorticoids (n = 110). Main Outcome Measures Recovery of HPA axis function. Results SST 30-minute cortisol levels above or below 350 nmol/L (12.7 μg/dL) best predicted HPA axis recovery [area under the curve (AUC) receiver operating curve (ROC) = 0.85; median recovery time: 334 vs 1368 days, P = 8.5 × 10-13]: 99% of patients with a 30-minute cortisol >350 nmol/L recovered adrenal function within 4 years, compared with 49% in those with cortisol levels

Objective — to estimate functional status of hypothalamo-pituitary-adrenal axis of pregnant women with regard to their psychoemotional status. Material and methods. There were examined 86 pregnant women in ІІ and ІІІ trimester (22-33 weeks). The main group comprises 60 pregnant women with medium and high level of state anxiety. The control group comprises 26 pregnant women with anxiety level of 30 points and less that stipulates the low level of state anxiety. Spielberger-Hanin scale was used for estimation of state anxiety and trait anxiety. Quantitative assessment of concentration of adrenocorticotropic hormone, cortisol, free testosterone, androstenedione, dehydroepiandrosterone sulphate and 17-α-ОН-progesterone hormones in blood plasma was determined by using the method of enzyme immunoassay with SIRIO S device. Results. Comparing concentrations of adrenocorticotropic hormone, 17-α-ОН-progesterone, free testosterone, androstenedione, there was not revealed statistically reliable difference (p>0.05) between pregnant women with medium-high and low levels of state anxiety. However availability of correlation between trait anxiety and level of adrenocorticotropic hormone both in the main group (r=+0.381, p0.05) can indicate some mutual influences. Analyzing the level of cortisol and dehydroepiandrosterone sulphate there was revealed statistically reliable prevalence of their content among anxious pregnant women in comparison with those of low level of state anxiety. Availability of correlation between state anxiety and cortisol level is confirmed by the positive correlation (r=+0.704, p0.05) as to their correlation in both groups as well as availability of the positive correlation both in the main group (r=+0.256, p0.05) for the level of adrenocorticotropic hormone, 17-α-ОН-progesterone, androstenedione and free testosterone with regard to anxiety level. However gestation course of anxious pregnants is accompanied by statistically reliable cortisol concentration increase (p

Anorexia nervosa (AN) is an eating disorder, mainly affecting women, with a lifetime prevalence of about 1%, that can run a chronic course. While an effective pharmacotherapy is lacking, it is hypothesized that the progesterone and type II glucocorticoid receptor antagonist mifepristone (RU486) might be useful, as it is well known that the hypothalamo-pituitary-adrenal axis (HPA) is activated in AN. Even if secondary to the eating disorder, an active HPA axis may contribute to maintaining the neuroendocrine, emotional and behavioral effects observed in AN. More specifically, it is suggested that the HPA axis interacts with limbic structures, including the insular and prefrontal cortices, to uphold the changes in interoceptive and emotional awareness seen in AN. As such, it is proposed that mifepristone (RU486) reverses these effects by acting on these limbic regions. In conclusion, the theoretical efficacy of mifepristone (RU486) in improving symptoms of AN should be tested in randomized clinical trials.

Context Secondary adrenal insufficiency is a potential complication of transsphenoidal adenomectomy (TSA). Most centers test recovery of the hypothalamo-pituitary-adrenal (HPA) axis after TSA, but, to our knowledge, there are no data predicting likelihood of recovery or the frequency of later recovery of HPA function. Objective To assess timing and predictors of HPA axis recovery after TSA. Design Single-center, retrospective analysis of consecutive pituitary surgeries performed between February 2015 and September 2018. Patients Patients (N = 109) with short Synacthen test (SST) data before and at sequential time points after TSA. Main outcome measures Recovery of HPA axis function at 6 weeks, and 3, 6, and 9 to12 months after TSA. Results Preoperative SST indicated adrenal insufficiency in 21.1% Among these patients, 34.8% recovered by 6 weeks after TSA. Among the 65.2% (n = 15) remaining, 13.3% and 20% recovered at 3 months and 9 to 12 months, respectively. Of the 29% of patients with adrenal insufficiency at the 6-week SST, 16%, 12%, and 6% subsequently recovered at 3, 6, and 9 to 12 months, respectively. Preoperative SST 30-minute cortisol, postoperative day 8 cortisol, and 6-week postoperative SST baseline cortisol levels above or below 430 nmol/L [15.5 μg/dL; AUC ROC, 0.86]; 160 nmol/L (5.8 μg/dL; AUC ROC, 0.75); and 180 nmol/L (6.5 μg/dL; AUC ROC, 0.88), were identified as cutoffs for predicting 6-week HPA recovery. No patients with all three cutoffs below the threshold recovered within 12 months after TSA, whereas 92% with all cutoffs above the threshold recovered HPA function within 6 weeks (OR, 12.200; 95% CI, 5.268 to 28.255). Conclusion HPA axis recovery can occur as late as 9 to 12 months after TSA, demonstrating the need for periodic reassessment of patients who initially have SST-determined adrenal insufficiency after TSA. Pre- and postoperative SST values can guide which patients are likely to recover function and potentially avoid unnecessary lifelong glucocorticoid replacement.

Changes in the physiological, psychological, and behavioral manifestations of stress have been observed in association with increases in circulating oxytocin (OXT). Providing OXT intranasally has been shown to attenuate stressor-induced hypothalamo-pituitary-adrenal (HPA) axis activation in humans and rodents; however, anxiolytic effects may be context and species specific. The present study aimed to investigate the effect of intranasal OXT supplementation on stressor-induced activation of the HPA axis in beef cattle. We hypothesized that OXT would attenuate activation of the HPA axis, ultimately decreasing plasma cortisol and adrenocorticotropic hormone (ACTH). Twenty-eight Bos taurus heifers were blocked by bodyweight and randomly allocated to one of four treatment groups, in a 2 × 2 factorial arrangement: (1) saline, isolated, standing, and unrestrained (S-isolation stress [IS], 0.015 mL/kg BW 0.9% isotonic saline, n = 7); (2) saline, isolated, and restrained (S-restraint and isolation stress [RIS]; 0.015 mL/kg BW 0.9% isotonic saline; n = 7); (3) OXT, IS (OXT-IS, 0.3 IU/kg BW oxytocin; n = 7); and (4) OXT and RIS (OXT-RIS, 0.3 IU/kg BW oxytocin; n = 7). Oxytocin and saline were administered intranasally. Intranasal treatments were given followed by a waiting time of 30 min when each of the stress treatments was applied for 2 h. Blood samples were collected via jugular catheters directly after stressor application and every 10 min thereafter, for 2 h. Cortisol concentrations increased over time in animals exposed to RIS (P0.01) and decreased over time in animals exposed to IS (P0.01). Concentrations of ACTH decreased over time for the IS-treated heifers but remained elevated for the RIS-treated heifers (P0.01). Under the conditions of the present study, OXT treatment did not affect measured indicators of HPA axis activation. A treatment × time interaction (P0.01) was detected for OXT, such that OXT heifers exhibited greater initial OXT concentrations followed by a decline; saline-treated heifers had consistently stable oxytocin concentrations. The RIS-treated heifers increased their glucose (P0.01) and lactate (P0.01) concentrations throughout the application of the stressors compared with the IS-treated heifers. Overall, restraint stress increased cortisol and oxytocin in B taurus heifers compared with heifers subjected only to isolation. Finding a more intermediate stress model may better allow for detection of the effects of oxytocin on the stress response.

Aim: Adolescence is an important period of development and during this period young people are more susceptible to mental illnesses. Therefore, a comprehensive knowledge of the factors that mediate stress response can help developing our understanding of these diseases. The aim of this study is to examine the activity of hypothalamo–pituitary–adrenal axis and determine factors affecting this activity in adolescents. Material and Methods: The adolescents between the ages of 14 and 17, who participated in the official amateur tennis tournament, were included in the study. The data form, including questions for the assessment of the stress level and sociodemographic variables was filled. Then, salivary cortisol levels were measured before (-5 minutes) and after (+5 minutes) the first match of the official tennis tournament. Results: The mean salivary cortisol levels were 40.8±53.8 ng/ml, before the game and 98.8±150.5 ng/ml, after the game (p=0.008). The salivary cortisol levels were statistically higher, after the game, in males, those who won, and those who felt anxious compared the before. Conclusion: The results of this study showed that salivary cortisol level can be used in the assessment of stress response in adolescents and various factors such as gender, mood, and state of winning are effective on cortisol response.

Early life experiences can affect the function of the hypothalamo-pituitary-adrenal (HPA) axis of vertebrates, with potential fitness consequences later in life. In altricial species, for example, variation in parental behavior, e.g. brooding or feeding, can modify the activity of the HPA axis of the young by altering their exposure to noxious stimuli as the young develop in the nest. We have shown that a drop in the body temperature of eastern bluebird (Sialia sialis) chicks, such as occurs when females are away from the nest, elevates their blood corticosterone levels. If repeated during the early days of their development, cooling bouts also reduce the chicks’ later corticosterone secretion in response to handling. Thus, variation in maternal behavior has the capacity to shape the function of the chicks’ HPA axis. To better understand how maternal absence from the nest activates the HPA axis of bluebird chicks, we experimentally mimicked the cooling that occurs when the female is away from the nest, and investigated a) the age at which the HPA axis becomes capable of responding to cooling by increasing corticosterone secretion, b) whether corticosterone secretion remains elevated throughout long periods of cooling, and c) whether fasting (also potentially associated with maternal absence) interacts with cooling to affect corticosterone secretion. Cooling for 18 min significantly elevated circulating corticosterone levels of chicks as young as 4 days post-hatch, indicating that their HPA axis is sensitive to cooling very early in life. Corticosterone levels remained elevated throughout longer bouts of cooling. However, a 1-hr period of fasting had no effect on corticosterone secretion, regardless of whether chicks were cooled or not. Collectively, these data demonstrate that variation in maternal brooding behavior can substantially modify the corticosterone profiles of chicks during early postnatal development, and that chick temperature is likely the main driver of this.

Introduction: Postgraduate (PG) training programme in medical field is a transitional period for PG students. They are expected to be able to present state of the art information for the decisions taken for treating the patients. It requires extraordinary time demand leading to physical exhaustion. Academic, professional and personal factors cause stress in day to day life. Sustained stress leads to increased rate of anxiety, depression and suicidal tendencies. Many studies have been done to evaluate stress in undergraduate medical students but very few studies have been done in PG medical students in India. Aim: To evaluate and compare stress amongst I and III year post graduate students by Perceived Stress Scale (PSS) and by estimating the levels of salivary cortisol. Materials and Methods: This was a cross-sectional observational study using self administered questionnaire. The study group consisted of 60 PG students (I year-30 students and III year-30 students). They were asked to complete a questionnaire which included personal data, academic problems, social support, and other stress inducing factors. Stress was measured by PSS score and estimation of salivary cortisol was done by ELISA. Salivary cortisol was analysed by unpaired t-test. Simple percentage analysis of PSS questionnaire was done. Results: Analysis of salivary cortisol levels and PSS score amongst I and III year PG students was statistically significant (p

Changes in the physiological, psychological, and behavioral manifestations of stress are observed in association with increases in circulating oxytocin. Providing oxytocin intra-nasally attenuates stressor-induced hypothalamo-pituitary-adrenal (HPA) axis activation in humans and rodents. The present study was conducted to investigate effects of intra-nasal oxytocin supplementation on stressor-induced activation of the HPA axis in beef cattle. We hypothesized that oxytocin would attenuate activation of the HPA axis, ultimately decreasing plasma cortisol. Bos taurus heifers (n = 28) were blocked by bodyweight and randomly allocated to one of four treatment groups, in a 2 × 2 factorial arrangement: 1) Saline, isolated, standing, and unrestrained (S-IS, 0.015mL/kg BW 0.9% isotonic saline, n = 7); 2) Saline, isolated, and restrained (S-RIS; 0.015 ml/kg BW 0.9% isotonic saline; n = 7); 3) Oxytocin, IS (OXT-IS, 0.3 IU/kg BW oxytocin; n = 7); and 4) Oxytocin and isolated and restrained (OXT-RIS, 0.3 IU/kg BW oxytocin; n = 7). Oxytocin and saline were administered intra-nasally. Appropriate stressors were applied 30 minutes following intra-nasal treatment. Blood samples were collected directly following imposing the stressor, and every 10 minutes thereafter, for 2 h. Cortisol concentrations increased over time in animals exposed to restraint and isolation stress (P < 0.01) and decreased over time in animals exposed to isolation stress (P < 0.01). In the present study, oxytocin did not affect measured indicators of HPA axis activation. Greater plasma oxytocin concentrations were observed in restrained animals administered saline, compared with their standing counterparts administered oxytocin (P < 0.01), indicating some endogenous release of oxytocin in response to restraint stress. Overall, restraint stress increased cortisol and oxytocin in Bos taurus heifers compared with heifers subjected only to isolation. Finding a more intermediate stress model may allow for more precise detection of effects of oxytocin on the stress response.

This study evaluates the efficacy of mifepristone on weight restoration in rats subjected to dietary restriction and methylphenidate administration. 25 female rats aged between 9 and 12 months were divided into 2 groups: 5 controls (exposed only to dietary restriction) and 20 rats that were administered 5 mg/kg/d of methylphenidate before meal exposure, for 36 days. Among rats who responded to methylphenidate (weight loss of 15-25%) weeks after its administration, a group of 6 rats continued to receive only methylphenidate ("Met" group), and another group received 10 mg/kg/d of mifepristone in addition to methylphenidate for 18 days ("Met+Mif" group; n = 6). The mean weight of the "Met+Mif" group remained significantly lower when compared to the control group (87.63 ± 2.83% vs 96.29 ± 3.26%; p 0.001 respectively) but was significantly higher than that of the "Met" group (87.63 ± 2.83% vs. 80.61 ± 3.52%; p 0.001 respectively). Plasma concentrations of adiponectin and gene expression of its receptors in rats brain were significantly higher in the "Met" group as compared to the "Met+Mif" and control groups (p 0.01). Accordingly, mifepristone reduces HPA axis activation and restores weight through adipose tissue recovering. It might be considered a promising treatment for anorexia nervosa patients in future studies.

Heterogeneous hypothalamo-pituitary-adrenal (HPA) system dysregulation has been shown in multiple sclerosis (MS), and cross-sectional studies suggested increasing hyperactivity with longer, progressing disease. Longitudinal studies to confirm this hypothesis and to study the impact of disease modifying treatment (DMT) have not been performed.In order to determine the longitudinal evolution of HPA system activity in patients with MS, we performed an open follow-up evaluation of sixty patients with definite MS. Patients were untreated at baseline; at follow-up, 40 received DMT. From the combined dexamethasone/CRH test, performed at baseline and follow-up, we derived neuroendocrine indicators (maximum, maximum rise, mean location and area under the curve) for cortisol, ACTH and ACTH/cortisol ratio.In 20 patients who remained untreated (test-retest interval 28.8 ± 5.4 months), ACTH/cortisol ratios decreased significantly, driven by both mild increase in cortisol and reduction of ACTH secretion. In 40 patients with DMT (test-retest interval 15.5 ± 2.5 months), secretion of cortisol, ACTH and ACTH/cortisol ratios did not change significantly. There was significant, moderate correlation between baseline and follow-up tests for cortisol, but not for ACTH indicators. In untreated, but not in treated patients, change in ACTH/cortisol ratios showed moderate inverse correlation to the time interval between tests (Pearson: beta -0.52 to -0.56, p0.05); the relation to progression of neurological disability was not significant.HPA axis activation in untreated MS drifts from hypothalamo-pituitary to more adrenal activation, consistent with adrenal sensitization or hypertrophy due to chronic HPA axis activation. HPA system regulation remains more stable in MS patients on DMT.

The interrelations of circannual rhythms of the functional states of pineal gland, hypothalamo-pituitary-adrenal axis, and thymus in healthy 20–79-year-old men and women were studied. Fluctuations of melatonin, ACTH, cortisol, and serum thymic factor that are characteristic of young 20–29-year-old people changed with aging (changes of amplitudes of seasonal peaks of hormones, shift of the seasonal acrophase, monotony). Rhythmicity disorder of studied organs in men was observed earlier than in women (pineal gland and ACTH of hypophysis after 30; thymus and adrenal cortex after 40) and more prominent. The age-specific desynchronosis of melatonin production in the pineal gland is an important pathogenetic part in disturbance of rhythmicity of hypothalamo-pituitary-adrenal system and thymus.

Exercise represents a potent physiological stimulus upon the hypothalamo-pituitary adrenal (HPA) axis. Two major factors modulate the HPA axis response to exercise: intensity and duration. Endurance training per se does not induce permanent hypercortisolism as endurance-trained subjects have similar biological markers of HPA axis activity in resting condition as healthy untrained men. However, during a challenge of the HPA axis, endurance-trained subjects demonstrate an adaptation of the HPA axis activity to repeated exercise resulting from decreased tissular sensitivity to glucocorticoids. A great diversity of other mechanisms is involved in this adaptation, acting potentially at all levels in the cascade and leading to the biological effects of cortisol.

Some evidence suggests that there might be a species difference in the effect of intracerebroventricularly administered (ICV) prolactin-releasing peptide (PrRP) between rodents and sheep. We compared the levels of cortisol (CORT) and prolactin (PRL), rectal temperature (RT) and behavioral responses to ICV bovine PrRP (bPrRP) in steers. ICV bPrRP (0.2, 2 and 20 nmol/200 µL) tended to evoke a dose-related increase in CORT concentrations and 0.2 nmol of bPrRP induced transient increase in PRL concentrations. A significant time-treatment interaction was observed for the percent change of CORT (P

Evaluation of the HPA axis is still a challenge; due to different sensitivities and stimulation efficiencies of dynamic tests, lack of standard assays for cortisol measurement and lack of data regarding the effects of age and gender on the results of the HPA axis evaluation with different dynamic tests. This study was performed to compare 1 mu g ACTH, 250 mu g ACTH and glucagon tests in the evaluation of HPA axis. The study was carried out on 55 healthy individuals (28 men, 27 women). 10-12 volunteers were included from every decades between 20 and 70 years. Low dose short synacthen test (1 mu g ACTH), standard dose short synacthen test (250 mu g ACTH) and glucagon tests were performed consecutively. The mean peak cortisol response to standard dose ACTH stimulation test was found to be significantly higher than the low dose ACTH and glucagon stimulation tests. The mean peak cortisol responses to low dose ACTH and the glucagon stimulation tests were not significantly different. The mean peak cortisol responses did not differ significantly between different age or sex groups. The lowest peak cortisol responses obtained after low dose ACTH and glucagon stimulation tests were 12.5 and 9.1 mu g/dl respectively in the volunteers who all had cortisol responses higher than 20 mu g/dl after standard dose ACTH stimulation test. The lowest cortisol responses obtained during 250 mu g ACTH, 1 mu g ACTH and glucagon stimulation tests were found to be 20.1, 12.5 and 9.1 mu g/dl in a known group of healthy people. So the consideration of appropriate hormonal cut-off levels for each test seems reasonable. The age, sex and body mass indeces were not shown to affect the cortisol response to dynamic stimulation tests.

Studies in arginine vasopressin (AVP)-deficient Brattleboro rats suggest that AVP is the predominant secretagogue during the perinatal period. Here we tested the hypothesis that congenital lack of vasopressin differentially modifies the stress reactivity of male and female rat pups. Vasopressin-producing (heterozygous, AVP+) and AVP-deficient (AVP-) Brattleboro rat pups of both genders were used. In 10-day-old pups, 24-h maternal separation and single, as well as repeated, ether inhalation induced remarkable adrenocorticotropin (ACTH) elevation only in AVP+ pups, supporting the role of vasopressin in hypothalamo-pituitary-adrenal (HPA) axis regulation. Surprisingly, the corticosterone elevations were even more pronounced in AVP- pups, suggesting the possibility of an ACTH-independent corticosterone-secretion regulation. In the case of maternal separation, both the plasma ACTH and corticosterone levels were higher in females than in males, while in case of ether inhalation only the ACTH levels were higher in females. Gender did not influence the stress reactivity or the effect of the genotype. We conclude that the gender of the pups did not profoundly influence HPA axis activity (the mechanism seems to be the same), but in contrast to the general view, we suggest that the females have a more active HPA axis than the males already during the neonatal period. However, the resting corticosterone elevation-well known in adult females- is missing.

Objective: The amygdala (AMG) plays a facilitatory role in the hypothalamic-pituitary-adrenal (HPA) axis. The effect of the AMG on the negative feedback exerted by glucocorticoids (GC) is not clear. We investigated the effect of repeated electrical stimulation of the AMG on the feedback action of GC upon the adrenocortical (AC) response to stressful stimuli. Methods: Rats received electrical stimulation into the central amygdalar nucleus once daily for 4 days. At days 5 and 12 after the onset of stimulation, rats were treated with dexamethasone (Dex) or vehicle and were exposed to either photic or acoustic stress stimuli, and serum corticosterone (CS) was measured. In another group of rats, we measured the binding of Dex to the hippocampal cytosol at 5 and 12 days after the AMG stimulation. Results: At 5 and 12 days after the onset of stimulation or a sham control, stress increased the serum CS level. In the sham group, Dex completely inhibited the CS response, but at 5 days after stimulation, it was significantly less effective in doing this. At day 12, Dex was as effective as in the control group. AMG stimulation delayed the return of CS response to basal levels and caused a significant decrease in the binding capacity of Dex to hippocampal cytosol. Conclusion: Electrical stimulation of the AMG caused a transient impairment of the feedback action of GC upon the stress response. This effect may be due to the decrease in hippocampal corticosteroid receptors. This suggests that the impaired GC feedback caused by AMG stimulation may be involved in the facilitatory effect of the AMG on the function of the AC axis.

We investigated the effect of the presence and absence of lambs and suckling by lambs to attenuate activation of the hypothalamo-pituitary-adrenal (HPA) axis to isolation and restraint stress in lactating sheep. In experiment 1, blood samples were collected every 10 min from nonlactating (n = 5) and lactating (n = 5) ewes for 4 h before and during stress. In experiment 2, ewes (n = 6) were allocated to 1) nonlactating, 2) lactating with lambs absent, 3) lactating with lambs present but unable to suckle, and 4) lactating with lambs present and able to suckle. Blood samples were collected over 8 h with no stress (control day) and for 4 h before and 4 h during stress (stress day). In experiment 1, the mean (±sem) cortisol concentrations increased significantly (P < 0.05) in nonlactating ewes during stress but did not change in lactating ewes. In experiment 2, cortisol did not vary on the control day or pretreatment of the stress day but increased (P < 0.05) during stress in all groups except lactating ewes with lambs present and able to suckle. The greatest cortisol response occurred in nonlactating ewes followed by lactating ewes with lambs absent and lactating ewes with lambs present but unable to suckle. During stress, the ACTH concentrations increased (P < 0.05) in nonlactating ewes and lactating ewes with lambs absent but not in lactating ewes with lambs present. We conclude that the activity of the HPA axis during isolation and restraint is reduced in lactating ewes and that the presence of lambs increases this level of attenuation.

The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly flexible operating characterisitics. Major drivers include two circadian drivers, two extra-hypothalamic networks controlling top-down (psychogenic) and bottom-up (systemic) threats, and two intra-hypothalamic networks coordinating behavioral, autonomic, and neuroendocrine outflows. These various networks jointly and flexibly control HPA axis output of periodic (oscillatory) functions and a range of adventitious systemic or psychological threats, including predictable daily cycles of energy flow, actual metabolic deficits over many time scales, predicted metabolic deficits, and the state-dependent management of post-prandial responses to feeding. Evidence is provided that reparation of metabolic derangement by either food or glucocorticoids results in a metabolic signal that inhibits HPA activity. In short, the HPA axis is intimately involved in managing and remodeling peripheral energy fluxes, which appear to provide an unidentified metabolic inhibitory feedback signal to the HPA axis via glucocorticoids. In a complementary and perhaps a less appreciated role, adrenocortical hormones also act on brain to provide not only feedback, but feedforward control over the HPA axis itself and its various drivers, as well as coordinating behavioral and autonomic outflows, and mounting central incentive and memorial networks that are adaptive in both appetitive and aversive motivational modes. By centrally remodeling the phenotype, the HPA axis provides ballistic and predictive control over motor outflows relevant to the type of stressor. Evidence is examined concerning the global hypothesis that the HPA axis comprehensively induces integrative phenotypic plasticity, thus remodeling the body and its governor, the brain, to yoke the needs of the body to the wants of the mind. Adverse side effects of this yoking under conditions of glucocorticoid excess are discussed.

Objectifs. - Evaluer le risque d'insuffisance surrenalienne durant le suivi medical reglementaire organise par la Federation francaise de cyclisme en fonction de la prise de glucocorticoides. Synthese des faits. - Les glucocorticoides de synthese sont des medicaments tres utilises en milieu sportif, et peuvent entrainer des complications severes. En 2001 et 2002, 659 cyclistes elites ont ete surveilles par dosage de la cortisolemie basale. Trente-quatre (5,2 %) avaient un cortisol bas (< -2 DS), et donc une suspicion d'insuffisance surrenalienne. Sur 15 de ces cyclistes qui ont eu une exploration des surrenales par un test au synacthene, huit avaient un test perturbe. En 2002, un autoquestionnaire a montre que 15,8 % des cyclistes avaient eu une corticotherapie et a permis d'analyser les modes de prescription. Conclusion. - Notre etude confirme l'interet du dosage du cortisol plasmatique pour depister et reduire les risques d'insuffisance surrenalienne chez les cyclistes. Ce dosage devrait etre etendu aux autres disciplines a risque.

Traitement buccal avec SRP299 (Mycobacterium vaccae tue) inhibant la maladie parodontale experimentale chez le rat Wistar Le Mycobacterium vaccae injecte en sous-cutane a prouve son efficacite a prevenir et traiter la maladie parodontale (PD) induite par ligatures chez le rat Wistar. Puisque les mycobacteries sont prelevees via les patchs de Peyers dans l'intestin, l'habilite du SRP299 (M. vaccae tue) a empecher la PD par ligature chez le rat Wistar et a moduler les reponses de la corticosterone et de la cytokine qui les accompagnent a ete testee. Une dose buccale simple de SRP299 (1 mg) a ete administree quatorze jours avant le placement des ligatures. PD a ete enregistree lorsque les ligatures sont restees en place pendant 56 jours. Le SRP299 buccal a reduit la perte osseuse (p = 0.036, RX; p = 0.061, histometrie) et la perte de fibre, tant dans les sites ligatures (p = 0.0047) que les controles (p = 0.005), et aussi la teneur en TNF-alpha (p = 0.0137) et la corticosterone (p = 0.048) induite par l'endotoxine intraperitoneale (LPS). Le SRP299 administre par voie buccale diminue la perte de fibre et d'os induits par ligature dans le modele present. Cet effet peut etre attribue a l'habilite connue du SRP299 a susciter les cellules T de regulation bien que ce mecanisme ne pouvait pas etre etudie dans cette etude. Les rats traites avait egalement moins d'HPA excitables. L'axe HPA lorsqu'il est hyperactive est connu comme etant un facteur de risque dans la PD humaine. Des essais cliniques de SRP299 dans la PD humaine sont maintenant justifies.

Background/aim: To investigate prospectively the hypothalamo-pituitary-adrenal (HPA) axis by adrenocorticotropic hormone (ACTH) stimulation test. Materials and methods: Tularemia was diagnosed according to guidelines. An ACTH stimulation test (1 µg) and a dexamethasone suppression test (DST; 1 mg) were performed in patients in the acute phase of tularemia before antibiotic treatment and in the chronic phase. Results: Nineteen patients (mean age: 41.0 ± 13.2 years; 57.9% female) with tularemia were enrolled in the study in 2011 and 2012. Cortisol response to ACTH stimulation test was sufficient in all patients during the acute phase. After the DST, the cortisol was not suppressed during the acute phase in only one patient. The median control time of 11 patients after acute tularemia was 13 months. During the chronic phase, cortisol response to ACTH stimulation was normal in all patients, and after DST cortisol was suppressed in all patients. The peak cortisol level after the ACTH stimulation test in the acute phase was higher than that in the chronic phase, but the difference was not statistically significant. Conclusion: The HPA axis of patients with tularemia was not significantly affected in the acute and chronic phases.

Adrenal insufficiency (AI) is a wellknown cause of potentially life-threatening disorders. Defects at each level of the hypothalamic-pituitary-adrenal axis can impair adrenal function, leading to varying degrees of glucocorticoid (GC) deficiency. Iatrogenic AI induced by exogenous GCs is the most common cause of AI. The criteria for the diagnosis and management of iatrogenic AI, neonatal AI, and critical illness-related corticosteroid insufficiency (CIRCI) are not clear. We reviewed the recent original publications and classical data from the literature, as well as the clinical, diagnostic and management strategies of pediatric AI. Practical points in the diagnosis and management of AI with an emphasis on iatrogenic AI, neonatal AI, and CIRCI are provided. Given the lack of sensitive and practical biochemical tests for diagnosis of subtle AI, GC treatment has to be tailored to highly suggestive clinical symptoms and signs. Treatment of adrenal crisis is well standardized and patients almost invariably respond well to therapy. It is mainly the delay in treatment that is responsible for mortality in adrenal crisis. Education of patients and health care professionals is mandatory for timely interventions for patients with adrenal crisis.

The sections in this article are: 1 Regulation of Function in the Hypothalamo-Pituitary-Adrenal Axis 1.1 Corticosteroid Receptors: Feedback Control of the Hypothalamo-Pituitary-Adrenal Axis by Exogenous Corticosteroid Treatment 1.2 Stressor-Induced Endogenous Corticosteroid Secretion and Feedback Control 1.3 Chronic or Repeated Stressors Induce Facilitated Responses 1.4 Diurnal Rhythms and Responsivity 2 Acute Versus Chronic Stressors: Effects on Activity in the Hypothalamo-Pituitary-Adrenal Axis 2.1 Acute Responses to Stress 2.2 Adaptations to Intermittent Stimuli 2.3 Adaption to Chronic, Sustained Stimuli 3 Corticosteroids, Stress, and Energy Balance 3.1 Energy Acquisition 3.2 Energy Disposition 4 Chronic Stress in Humans

This paper reviews studies of the hypothalamo-pituitary-adrenal (HPA)-axis activity in patients with affective disorders. It is concluded that, despite methodological drawbacks in most studies, dysregulation of the HPA axis seems to be a consistent finding in a proportion of patients with affective disorder. The HPA axis is a complex neuroendocrine network with multiple integrated levels of control, and it is likely that the dysregulation involves abnormalities at several sites within the axis. At present, it is not clear whether the abnormalities are related to the affective episodes only or to the disorder itself. There is a need for prospective studies of larger samples of patients to be followed during successive affective episodes with a combination of measurements of the HPA-axis activity and brain imaging.

The temporal and quantitative interrelationships between the hypothalamo-pituitary-adrenal (HPA) axis activity and the level of central arousal were studied in 10 healthy young men during daytime wakefulness. Two experimental sessions were conducted randomly between 09.00 and 18.00 h, once after nocturnal sleep and once after a night of total sleep deprivation. Spectral analysis of serial waking electroencephalography (EEG) from a short target fixation task repeated every 10 min was undertaken, along with an estimation of cortisol secretory profiles by deconvolution of plasma radioimmunoassay measures obtained from continuous blood withdrawal with regular sampling at a 10-min interval. Following nocturnal sleep, a temporal association between the HPA axis activity and the waking EEG activity was found, cortisol secretory rate following changes in frontal gamma (20–45 Hz) band power by 10 min (average R = 0.458, p < 0.001). Although it remained significant (average R = 0.276, p < 0.05), the association strength decreased significantly following total sleep deprivation (p < 0.05, Wilcoxon test). Cortisol plasma level, secretory rate and pulse amplitude were increased as well as waking EEG power in the delta (0.5–5.5 Hz), theta (5.5–8.5 Hz) and gamma frequency bands (all p values

Gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus is pivotal to the regulation of reproductive physiology in vertebrates. GnRH and the reproductive axis, in general, can be inhibited during periods of stress or injury. Stress, in the form of mechanical, psychological or immunological insult to an organism results in the activation of the hypothalamo-pituitary-adrenal (HPA) axis initiated by the hypothalamic release of corticotropin-releasing factor (CRF). Recent studies indicate that CRF may act either directly on the GnRH neuron to down-regulate GnRH synthesis, or indirectly via a β-endorphin-mediated pathway. Moreover, in vitro studies suggest that CRF-related peptides can increase the sensitivity of the GnRH neuron to prolactin by increasing the synthesis of the prolactin receptor.

Many of the pro-inflammatory cytokines which are released in response to immune/inflammatory insults exert marked stimulatory influences on the hypothalamo–pituitary–adrenocortical (HPA) axis; they thus provoke the release of glucocorticoids which, in turn, temper the ensuing immune–inflammatory response and thereby complete a homeostatic neuroendocrine–immune regulatory loop. This article reviews the putative mechanisms by which cytokines, released acutely in response to such insults, activate the HPA axis, placing particular emphasis on the actions and interactions of tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) and on the counter-regulatory mechanisms that are in place.

We propose a dynamical model for the pulsatile secretion of the hypothalamo-pituitary-adrenal axis. This model takes into account both the binding of hormone with proteins in the plasma and tissues and mutual interactions of the hormones in the system. The deductions from this model are in good agreement with experiment results.