Increased Cortisol Release Research Articles

Multiple sclerosis with comorbidity depression and its association with vitamin D deficiency in a narrative review of the current literature

Over the past decade, knowledge of the pathophysiology and immunology of multiple sclerosis (MS) and depression, and the complex links to vitamin D (VitD) balance, has increased rapidly. Both diseases are characterized by an imbalance of proinflammatory and antiinflammatory cytokines, increased serum neurofilament light chains (sNfLs), disruption of the blood-brain barrier (BBB), abolition of the physiological function of the various types of microglia (MG), decreased calcidiol-serum levels, and disorders of the gut microbiome in combination with hyperactivity of the hypothalamic-pituitary-adrenal (HPA)-axis/microbiome-gut-brain-axis characterized. In depression, stress initiates cellular and molecular changes in the brain via increased cortisol release in the HPA-axis. Microglial activation and neuronal damage as well as dysregulation of neuroplastic and neurotrophic factors complete the spectrum of pathological damage. It is shown that gut dysbiosis leads to increased gut permeability, which favors endotoxemia and ultimately paves the way to systemic inflammation. A VitD supplementation could restore the balance of microorganisms in the intestine and reduce the inflammatory processes at various levels. VitD promotes regulatory T cell (Treg) proliferation, inhibits the expression of T helper 1 (Th1) cells and Th17 immune cells, and inhibits proinflammatory interleukin-17 (IL-17). 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] reduces also the secretion of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Increased calcitriol levels lead to a reduction in MG activation, oxidative stress, and lower BBB permeability. An early, permanent, daily sufficient VitD supplementation as an add-on therapy under control of the serum 25-hydroxyvitamin D [s25(OH)D] levels is an essential therapeutic tool to slow down the disability caused by MS and thereby primarily prevent or reduce the stress and subsequently the manifestation of depression. Through the future continuous measurement of the biomarkers serum neurofilament ligth chains and glial fibrillary acidic proteins as well as the s25(OH)D level in MS and comorbidity depression, future therapy successes or failures can be avoided.

Orexin-A/OX1R is involved in regulation of autophagy to promote cortisol secretion in adrenocortical cell

BackgroundHypercortisolism has emerged as a prominent clinical condition worldwide caused by biochemical cortisol excess in patients, and optimization treatment is needed urgently in the clinic. Previously, we observed that orexin-A/orexin type 1 receptor (OX1R) promoted cell proliferation, inhibited apoptosis, and increased cortisol release in adrenocortical cells. However, the functions of orexin-A/OX1R on autophagy and its molecular mechanism are not known. MethodsTransmission electron microscopy and confocal microscope were performed to detect autophagosomes. Western blot were performed to detect autophagy proteins. The cortisol concentration was assessed with an ELISA. FindingsOur data demonstrated that orexin-A/OX1R activated the mammalian target of rapamycin/p70 ribosomal protein S6 kinase-1 pathway, thereby inhibiting autophagy in H295R cells and Y-1 cells. Furthermore, the orexin-A/OX1R-mediated suppression of autophagy played a crucial role in cortisol secretion. Mechanistically, the expression of 3β-hydroxysteroid dehydrogenase/isomerase, the rate-limiting enzyme in cortisol synthesis, was increased with autophagy inhibition mediated by orexin-A/OX1R. InterpretationThis study provided the evidence that orexin-A/OX1R participated in modulating mTOR/p70S6K1/autophagy signaling pathway to promote cortisol secretion in adrenocortical cell. The findings suggest the mechanistic basis for disorders of cortisol secretion, providing the potential therapeutic targets for hypercortisolism treatment. FundThis work was supported by National Natural Science Foundation of China (32170603, 31871286), the Doctoral Start-up Foundation of Liaoning Province (20180540008, 2019-BS-298), the Natural Science Foundation of Liaoning Province (2019-ZD-0779), and Shenyang Science and Technology Plan Fund Projects (21-173-9-28).

Impact of social exclusion on empathy in women with borderline personality disorder

Unstable interpersonal relationships and fear of abandonment are core symptoms of borderline personality disorder (BPD) that often intensify during stress. Psychosocial stress, which includes components of social exclusion and increases cortisol secretion, enhances emotional empathy in healthy individuals. Women with BPD, on the contrary, react with reduced emotional empathy. The aim of the present study was to investigate the effects of perceived social exclusion without accompanying cortisol increase on empathy in women with BPD and healthy women. To induce social exclusion, we randomized 98 women with BPD and 98 healthy women to either an exclusion or an overinclusion (control) condition of Cyberball, a virtual ball game. Subsequently, participants underwent the Multifaceted Empathy Test (MET), which assesses cognitive and emotional empathy. There was no increase in cortisol release after Cyberball. Cognitive empathy did not differ between groups or conditions. Women with BPD reported lower emotional empathy for positive emotions (group by valence interaction), but not for negative emotions. Exploratory analyses suggested that this effect might be more pronounced after social exclusion. Our results confirm previous findings that cognitive empathy does not differ between women with BPD and healthy women and extend this evidence to social exclusion. Emotional empathy in women with BPD seems to be more sensitive to the effects of stress or ambiguous social situations. Specifically, emotional empathy seems to be reduced for positive emotions, and might further decline after social exclusion. Empathic reactions to emotional stimuli of different valences and to specific emotions should be further investigated.

Acute and chronic effects of cortisol on milk yield, the expression of key receptors, and apoptosis of mammary epithelial cells in Saanen goats

Cortisol (CORT) induces mammary development in late gestation and is fundamental to the differentiation of mammary epithelial cells and lactogenesis. The objective of this study was to investigate the relationship between CORT, insulin, prolactin, growth hormone, and insulin-like growth factor-1 in milk as well as the effect of CORT on the expression of receptors of insulin (INSR), prolactin (PRLR), growth hormone (GHR); we also studied the insulin-like growth factor-1 (IGF1R), glucocorticoid (NR3C1), mineralocorticoid (NR3C2), B-cell lymphoma 2 (BCL2), BCL-2-like protein X (BAX) genes, and the apoptosis rate of mammary epithelial cells of lactating Saanen goats in vivo and in vitro. The following experiments were conducted: (1) comparing hormone release in milk and blood after ACTH or a placebo administration; (2) evaluating the effect of acute CORT increases in mammary gland expression and milk yield in vivo; and (3) evaluating the effect of a chronic increase in CORT concentration in epithelial mammary cell apoptosis in vitro. In vivo, ACTH administration significantly increased CORT release but did not affect insulin, prolactin, growth hormone, and insulin-like growth factor-1 release in plasma and milk versus placebo. The results show also that a low CORT release after ACTH administration increased the expression of GHR and PRLR genes in the mammary tissue. Indeed, CORT release significantly increased the milk yield from goats subjected to ACTH versus goats subjected to the placebo. However, a higher amount of CORT added in vitro upregulated the NR3C1, GHR, PRLR, and BAX genes and downregulated the IGF1R and INSR genes, which could negatively modulate the apoptosis of mammary epithelial cells. Finally, the effect of CORT in vivo after ACTH administration demonstrated the increased expression of the PRLR and GHR genes, which may improve epithelial cell responsiveness and be associated with the positive effect of CORT observed on milk yield at mid-end lactation.

Nesfatin-1 stimulates the hypothalamus-pituitary-interrenal axis hormones in goldfish

Stress in vertebrates is mediated by the hypothalamus-pituitary-adrenal (in mammals)/interrenal (in fish) (HPA/I) axis, which produces the corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and corticosteroids, respectively. Nesfatin-1, a novel anorexigenic peptide encoded in the precursor nucleobindin-2 (NUCB2), is increasingly acknowledged as a peptide that influences the stress axis in mammals. The primary aim of this study was to characterize the putative effects of nesfatin-1 on the fish HPI axis, using goldfish (Carassius auratus) as an animal model. Our results demonstrated that nucb2/nesfatin-1 transcript abundance was detected in the HPI tissues of goldfish, with most abundant expression in the pituitary. NUCB2/nesfatin-1-like immunoreactivity was found in the goldfish hypothalamus, pituitary, and interrenal cells of the head kidney. GPCR12, a putative receptor for nesfatin-1, was also detected in the pituitary and interrenal cells. NUCB2/nesfatin-1-like immunoreactivity was observed in ACTH-expressing pituitary corticotrophs. Acute netting and restraint stress upregulated nucb2/nesfatin-1 mRNA levels in the forebrain, hypothalamus, and pituitary, as well as crf and crf-r1 expression in the forebrain and hypothalamus. Intraperitoneal and intracerebroventricular administration of nesfatin-1 increased cortisol release and hypothalamic crf mRNA levels, respectively. Finally, we found that nesfatin-1 significantly stimulated ACTH secretion from dispersed pituitary cells in vitro. Collectively, our data provide the first evidence showing that nesfatin-1 is a stress responsive peptide, which modulates the stress axis hormones in fish.

Now or Later? Stress-Induced Increase and Decrease in Choice Impulsivity Are Both Associated with Elevated Affective and Endocrine Responses.

Exposure to acute stress elicit physiological and psychological responses that can impact decision-making, often expressed as an increased tendency to act in an impulsive manner following stress. Delay discounting (DD) task has emerged as a reliable measure of impulsive behavior in the form of choice impulsivity (CI). Interestingly, studies that examined the effect of acute stress on DD performance reported mixed results. To address this, we conducted a within-subject examination of the impact of acute stress on CI, focusing on individual differences in response patterns. One hundred and fifty healthy female participants completed the DD task twice, before and after undergoing an acute laboratory stress induction procedure. Saliva samples and self-report mood and affect measures were collected at four time points throughout the session. Fifty-nine matched healthy control participants completed only the DD task twice, with no stress in between. Results indicate that the acute stress procedure elicited the expected effects of increased cortisol release and increased negative mood and affect, at the group level. With respect to DD, stress indeed increased CI at the group level, yet participants differed in the magnitude and direction of this effect. Interestingly, regression analysis revealed quadratic relations between stress-induced changes in CI and cortisol release. Indeed, dividing the sample into three sub-groups based on the impact of stress on CI revealed that, compared to participants that exhibited no substantial change in their CI following stress, participants that exhibited either stress-induced increase or decrease in their CI also exhibited more stress-induced cortisol release, as well as more negative affect. Taken together, these findings suggest that elevated physiological and psychological responses to stress are associated with either increased or decreased choice impulsivity, thus depicting quadratic relations between stress and impulsivity.

Long-term heat stress at final gestation: physiological and heat shock responses of Saanen goats.

The long exposure to heat negatively changes performance and productivity of animals, particularly when heat stress is associated with gestation. Indeed, little is known about the negative effects of long-term heat stress on the final gestation of dairy goats. In this context, the physiological and cellular responses of Saanen goats submitted to heat stress (37°C from 10:00 to 16:00 h) were investigated from day 60th pre-partum to day 60th post-partum. At final gestation, 46 pregnant Saanen goats were randomly assigned to the treatments: control (CT; thermal neutral conditions) and heat stress (HS; climatic chamber). After partum, all experimental goats were maintained in thermal neutral conditions. The rectal, dorsal, mammary temperatures and respiratory frequency, cortisol release, milk yield, milk quality, and the genes HSP60, HSP70, HSP90, Glucocorticoid receptor and ACTHR. Goats subjected to HS showed significantly (P < 0.05) higher rectal, dorsal, and mammary temperatures and significantly mobilized the increase of respiratory frequency to lose heat as compared to CT goats. The HS challenge significantly increased cortisol release from day 15th pre-partum to day 15th post-partum. CT goats produced more milk than HS from weeks 4 to 10 of lactation (P <0.001), with no difference in milk quality. However, on day 15th post-partum, there was a significant effect of HS treatment on the expression of HSP70 and ACTHR genes as compared to CT treatment, confirming the long-term effect of HS on Saanen goats. In conclusion, the physiological parameters studied increased pre-partum in the hottest hour, and cortisol peaked on day 15 pre-partum for heat-stressed goats. Although on the 15th day post-partum, all goats were in thermal comfort, and the physiological parameters were within the normal range, the concentration of cortisol continued to be significantly higher for goats submitted to thermal stress. Indeed, milk yield was greater for goats subjected to pre-partum thermal comfort. Furthermore, the expression of HSP70 and ACTHR genes on peripheral blood mononuclear cells are interesting biomarkers for studying the long-term effect of heat stress on Saanen goats.

Is it getting in the hair? – Cortisol concentrations in native, regrown and segmented hairs of cattle and pigs after repeated ACTH administrations

Adrenocorticotropic hormone (ACTH) is part of the hypothalamic-pituitary-adrenal axis response to stress and induces the release of cortisol, which is commonly used as an indicator in stress and animal welfare research. In recent years, hair cortisol concentration (HCC) gained increasing importance as a promising retrospective indicator for stress in animals. Thus, the aim of our study was to validate HCC as a potential indicator of increased endogenous cortisol release in cattle and pigs by repeated ACTH administrations followed by cortisol analysis in different hair types. For this purpose, 34 cattle and 38 gilts were treated either with repeated i.m. injections of ACTH or saline every second day over a period of 4 weeks. Saliva samples were taken before and after injections once a week from selected animals to verify the endogenous cortisol response. At the end of the treatment (week 4) and after 8 and 12 weeks, samples of natural and regrown hair were taken from the caudo-dorsal region of the back and analyzed for cortisol concentrations. In addition, natural hair was sampled after 12 weeks and cut into segments prior to analysis. Treatment with ACTH revealed a significant increase in salivary cortisol after application in both species, although this increase was attenuated in pigs compared to cattle. In week 4, HCCs were significantly elevated in natural and regrown hair of ACTH-treated animals. In cattle, HCCs significantly increased after ACTH treatment in natural, regrown and segmental hair compared with control animals, indicating that HCC may be a promising indicator of stress, as cortisol levels in all hair types reflected the preceding period with increased cortisol release. In pigs, there were no differences in HCCs between treatments. This may be caused by the lower systemic cortisol response in pigs, but seasonally reduced hair growth and external cross-contamination of hair by saliva and urine under commercial husbandry conditions may also interfere with the validity of HCC in this species.

Road Transport of Late-Pregnant Mares Advances the Onset of Foaling

Cortisol is involved in the initiation of parturition and we hypothesized that increased maternal cortisol release advances the onset of foaling. Transport is a stressor for horses and induces an increase in cortisol release. To determine stress effects on the time of foaling, late-pregnant mares were transported by road for 3 hours (n = 12) or remained in their stable as controls (n = 4). Starting on day 325 of gestation, saliva and blood samples were taken for cortisol and progestin analysis, respectively. Fetomaternal electrocardiograms were recorded repeatedly. Mares were checked for impending parturition and changes in precolostrum pH. When pH decreased to 6.5, mares were either transported or left untreated. After birth, saliva was collected repeatedly from mares and their foals and heart rate (HR) was recorded. Foals were checked for maturity and health. Gestation length was 337 ± 2 days in stressed and 336 ± 2 days in control mares. Cortisol concentration increased from 3.3 ± 0.9 to 8.4 ± 0.8 ng/mL in transported mares (P < .001) and remained constant in controls. Maternal HR and heart rate variability (HRV) did not differ between groups and neither fetal HR nor HRV changed in response to transport. In transported mares, time from precolostrum decrease to parturition was shorter (40 ± 10 hours) than the respective time in controls (134 ± 49 hours, P < .01). Neither duration of foaling nor times to first standing and suckling of foals or the postnatum increase in HR and decrease in HRV differed between groups. In conclusion, transport-induced maternal cortisol release may have advanced the onset of foaling.

Controlled delay of the expulsive phase of foaling affects sympathoadrenal activity and acid base balance of foals in the immediate postnatal phase

Stress at foaling has been demonstrated to delay birth. In this study, we followed the hypothesis that even a short delay of foaling increases catecholamine and cortisol release in foals, induces acidosis and impairs neonatal adaptation. Foaling was prolonged for 5 min by transferring mares to an unfamiliar environment at rupture of the allantochorion (group delay, n = 6) while control mares (n = 5) were left undisturbed. In their foals, times from birth to first standing and first suckling, heart rate, heart rate variability (HRV) and salivary cortisol concentration were analysed. Blood for analysis of epinephrine, norepinephrine, hematology and blood gases was collected directly and 30 min after birth. Statistical comparisons were made by repeated measures ANOVA. Times to first standing and suckling did not differ between groups. Fetal heart rate remained unchanged during birth and increased within 15 min postnatum (p < 0.001) while HRV decreased during the first hour of life in foals of both groups (p < 0.05). Immediately after birth, actual base excess was lower in foals with delayed birth than in control foals (p < 0.05). Epinephrine concentration immediately after birth was higher in group delay foals and increased from 0 to 30 min after birth in control foals (time p < 0.001, time x group p = 0.001). Cortisol concentration peaked at 1 h after birth in both groups (p < 0.001). Leukocyte and PMN count decreased from 0 to 30 min after birth (p < 0.001). In conclusion, a 5-min delay at foaling affected epinephrine release and acid base balance, but was without further effect on neonatal adaptation.

The effectiveness of noise interventions in the ICU.

Excessive noise has direct adverse physiological and psychological effects, and may also have indirect negative health consequences by reducing sleep quality and quantity. This review presents a synthesis of the epidemiology of noise in the ICU, and the potential interventions designed to attenuate noise and protect patients. Noise increases cortisol release, oxygen consumption, and vasoconstriction. ICU noise levels are excessive throughout the 24-h cycle, irrespective of level of intervention or whether the patient is in a side room or open ward. Direct measurement suggests that noise is a substantial contributor to poor sleep quantity and quality in the ICU and is frequently recalled by survivors of critical illness as a negative experience of ICU admission. Noise abatement, environmental masking and pharmacological interventions may all reduce the impact of noise on patients. However, the sustainability of behavioural interventions remains uncertain and high-quality evidence demonstrating the benefit of any intervention on patient-centered outcomes is lacking. Noise levels in the ICU are consistently reported to reach levels likely to have both direct and indirect adverse health consequences for both patients and staff. Noise reduction, abating the transmission of noise and pharmacological modulation of the adverse neural effects of noise are all potentially beneficial strategies, although definitive evidence of improved patient-centered outcomes is lacking.

Acute heat stress induces changes in physiological and cellular responses in Saanen goats

The relationships between rectal temperatures and physiological and cellular responses to heat stress can improve the productivity of Saanen goats in tropical environments. In this context, this study evaluated the physiological responses and gene expression of heat shock proteins (HSP60, 70, and 90) and genes related to apoptosis (Bax, Bcl-2, and p53) of Saanen goats subjected to acute heat stress. Ten health Saanen goats were exposed to solar radiation during 3 consecutive days. The expression of HSP60, HSP70, HSP90, Bax, Bcl-2, and p53 genes in blood leukocytes, rectal and superficial temperatures, respiratory frequency, cortisol, triiodothyronine, and thyroxine was measured at 06:00, 13:00, and 18:00h. In vitro, blood leukocytes were subjected to 38°C and 40°C for 3h to measure the expression of the same target genes. The temperature humidity index, measured from 12:00 to 15:00, was greater than 80 and black globe temperatures were greater at 40°C, indicating the intensity of the solar radiation. Although the solar radiation caused acute heat stress, increased cortisol release, and the expression of HSP60 and 70 in dry Saanen goats, the increased respiratory frequency and decreased T4 and T3 restored the homeothermy of the experimental goats. In vitro, the 40°C increased the expression of p53 (pro-apoptotic protein), Bcl-2 (anti-apoptotic protein), HSP60, HSP70, and HSP90, suggesting that these genes have protective functions. However, further studies are necessary to understand the physiological and cellular responses to heat stress.

Diet matters: Glucocorticoid-related neuroadaptations associated with calorie intake in female rhesus monkeys

Exposure to psychosocial stressors increases consumption of palatable, calorically dense diets (CDD) and the risk for obesity, especially in females. While consumption of an obesogenic diet and chronic stress have both been shown to decrease dopamine 2 receptor (D2R) binding and alter functional connectivity (FC) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc), it remains uncertain how social experience and dietary environment interact to affect reward pathways critical for the regulation of motivated behavior. Using positron emission tomography (PET) and resting state functional connectivity magnetic resonance neuroimaging (rs-fMRI), in female rhesus monkeys maintained in a low calorie chow (n = 18) or a dietary choice condition (chow and a CDD; n = 16) for 12 months, the current study tested the overarching hypothesis that the adverse social experience resulting from subordinate social status would interact with consumption of an obesogenic diet to increase caloric intake that would be predicted by greater cortisol, lower prefrontal D2R binding potential (D2R-BP) and lower PFC-NAcc FC. Results showed that the consequences of adverse social experience imposed by chronic social subordination vary significantly depending on the dietary environment and are associated with alterations in prefrontal D2R-BP and FC in NAcc-PFC sub-regions that predict differences in caloric intake, body weight gain, and fat accumulation. Higher levels of cortisol in the chow-only condition were associated with mild inappetence, as well as increased orbitofrontal (OFC) D2R-BP and greater FC between the NAcc and the dorsolateral PFC (dlPFC) and ventromedial PFC (vmPFC). However, increased cortisol release in females in the dietary choice condition was associated with reduced prefrontal D2R-BP, and opposite FC between the NAcc and the vmPFC and dlPFC observed in the chow-only females. Importantly, the degree of these glucocorticoid-related neuroadaptations predicted significantly more total calorie intake as well as more consumption of the CDD for females having a dietary choice, but had no relation to calorie intake in the chow-only condition. Overall, the current findings suggest that dietary environment modifies the consequences of adverse social experience on reward pathways and appetite regulation and, in an obesogenic dietary environment, may reflect impaired cognitive control of food intake.

Involvement of adenosine monophosphate activated kinase in interleukin-6 regulation of steroidogenic acute regulatory protein and cholesterol side chain cleavage enzyme in the bovine zona fasciculata and zona reticularis

In bovine adrenal zona fasciculata (ZF) and NCI-H295R cells, interleukin-6 (IL-6) increases cortisol release, increases expression of steroidogenic acute regulatory protein (StAR), cholesterol side chain cleavage enzyme (P450scc), and steroidogenic factor 1 (SF-1) (increases steroidogenic proteins), and decreases the expression of adrenal hypoplasia congenita-like protein (DAX-1) (inhibits steroidogenic proteins). In contrast, IL-6 decreases bovine adrenal zona reticularis (ZR) androgen release, StAR, P450scc, and SF-1 expression, and increases DAX-1 expression. Adenosine monophosphate (AMP) activated kinase (AMPK) regulates steroidogenesis, but its role in IL-6 regulation of adrenal steroidogenesis is unknown. In the present study, an AMPK activator (AICAR) increased (P < 0.01) NCI-H295R StAR promoter activity, StAR and P450scc expression, and the phosphorylation of AMPK (PAMPK) and acetyl-CoA carboxylase (PACC) (indexes of AMPK activity). In ZR (decreased StAR, P450scc, SF-1, increased DAX-1) (P < 0.01) and ZF tissues (increased StAR, P450scc, SF-1, decreased DAX-1) (P < 0.01), AICAR modified StAR, P450scc, SF-1 and DAX-1 mRNAs/proteins similar to the effects of IL-6. The activity (increased PAMPK and PACC) (P < 0.01) of AMPK in the ZF and ZR was increased by AICAR and IL-6. In support of an AMPK role in IL-6 ZF and ZR effects, the AMPK inhibitor compound C blocked (P < 0.01) the effects of IL-6 on the expression of StAR, P450scc, SF-1, and DAX-1. Therefore, IL-6 modification of the expression of StAR and P450scc in the ZF and ZR may involve activation of AMPK and these changes may be related to changes in the expression of SF-1 and DAX-1.

Does road transport influence plasma leptin concentrations in horses? Preliminary study

Abstract Transport is one of the most common stressors for horses leading to an increase in cortisol secretion. Cortisol promotes leptin synthesis and release. The aim of the study was to evaluate the effect of short transport on circulating leptin and cortisol concentrations. A total of 16 crossbred naïve horses (7 geldings, 9 mares) aged 2-11 years, and weighing 530-680 kg were included in the study. The horses were transported in a commercial horse-truck to an unknown holding pen for temporary housing. To measure plasma leptin and cortisol concentrations, three blood samples were collected from each horse: before transport, immediately after unloading from the truck, and nine hours after transport at the arrival point. Transport caused a significant increase in mean plasma cortisol concentration determined at unloading, and after nine hours of unloading, in comparison to values obtained before loading. Plasma leptin concentrations did not change during the study. In conclusion, transportation procedures did not influence plasma leptin concentration in horses, despite significantly increased cortisol release.

Academic stress-induced changes in Th1- and Th2-cytokine response

Psychological stress stimulates physiological responses releasing catecholamines and corticoids, which act via corresponding receptors on immune cells, producing a shift in the cytokine balance. These responses are variable depending on the nature of stressors. The effect of the academic stress on the production of the Th1-cytokines (TNF-α, IFN-γ, IL-1β, IL-2, IL-6 and IL-8) and Th2-cytokines (IL-1ra, IL-4, IL-5 and IL-10) on 35 medical/health sciences students after completing their questionnaires was investigated. Blood samples were taken at three stages; baseline stage at the beginning, midterm and final academic examination stages. Plasma cortisol and cytokines were measured during the three stages. The last two stages were compared with the baseline non-stress period. Results of the stress induced during the final examination stage were the highest with a significant increase in cortisol release, IL-4, IL-5 and IL-1ra release with a shift in Th1:Th2 cytokines balance towards Th2. Whereby, the midterm stage did not show significant reduction in Th1-cytokines except for TNF-α, with an increase in IFN-γ level that was reduced in the third stage. Th2 cytokine, IL-1ra, had positive correlations with Th1 cytokines; IL-2 and IFN-γ in the second stage and IL-6 cytokine in the third stage. Cortisol was positively correlated with IL-8 in the last stage and heart rates had negative correlation with IL-10 in the first and last stages. Findings of this study indicate that exam stress down-regulates Th1 with a selective up-regulation of Th2-cytokines. In conclusion, Cortisol might have a role in suppressing the release of Th1- mediated cellular immune response which could increase the vulnerability among the students to infectious diseases.

Distinct Trajectories of Cortisol Response to Prolonged Acute Stress Are Linked to Affective Responses and Hippocampal Gray Matter Volume in Healthy Females.

The development of robust laboratory procedures for acute stress induction over the last decades has greatly advanced our understanding of stress responses in humans and their underlying neurobiological mechanisms. Nevertheless, attempts to uncover linear relationships among endocrine, neural, and affective responses to stress have generally yielded inconsistent results. Here, 79 healthy females completed a well established laboratory procedure of acute stress induction that was modified to prolong its effect. Endocrinological and subjective affect assessments revealed stress-induced increases in cortisol release and negative affect that persisted 65 and 100 min after stress onset, respectively, confirming a relatively prolonged acute stress induction. Applying latent class linear mixed modeling on individuals' patterns of cortisol responses identified three distinct trajectories of cortisol response: the hyper-response (n = 10), moderate-response (n = 21), and mild-response (n = 48) groups. Notably, whereas all three groups exhibited a significant stress-induced increase in cortisol release and negative affect, the hyper-response and mild-response groups both reported more negative affect relative to the moderate-response group. Structural MRI revealed no group differences in hippocampal and amygdala volumes, yet a continuous measure of cortisol response (area under the curve) showed that high and low levels of stress-induced cortisol release were associated with less hippocampal gray matter volume compared with moderate cortisol release. Together, these results suggest that distinct trajectories of cortisol response to prolonged acute stress among healthy females may not be captured by conventional linear analyses; instead, quadratic relations may better describe links between cortisol response to stress and affective responses, as well as hippocampal structural variability.SIGNIFICANCE STATEMENT Despite substantial research, it is unclear whether and how individual neuroendocrine stress response patterns are linked to affective responses to stress and structural variability in neuroendocrine regulatory brain regions. By applying latent class linear mixed modeling on individuals' patterns of cortisol responses to a prolonged acute stressor, we identified three distinct trajectories of cortisol response. Relative to the group showing a moderate cortisol response, groups characterized by hyper and mild cortisol response were both associated with more negative affect. Moreover, a continuous measure of cortisol response showed that high and low levels of stress-induced cortisol release correlated with reduced hippocampal gray matter volume. Given that neuroendocrine stress responses are conceptualized as biomarkers of stress susceptibility, these insights may have clinical implications.

Sympathoadrenal balance and physiological stress response in cattle at spontaneous and PGF2α-induced calving

Increased cortisol release in parturient cows may either represent a stress response or is part of the endocrine changes that initiate calving. Acute stress elicits an increase in heart rate and decrease in heart rate variability (HRV). Therefore, we analyzed cortisol concentration, heart rate and HRV variables standard deviation of beat-to-beat interval (SDRR) and root mean square of successive beat-to-beat intervals (RMSSD) in dairy cows allowed to calve spontaneously (SPON, n = 6) or with PGF2α-induced preterm parturition (PG, n = 6). We hypothesized that calving is a stressor, but induced parturition is less stressful than term calving. Saliva collection for cortisol analysis and electrocardiogram recordings for heart rate and HRV analysis were performed from 32 hours before to 18.3 ± 0.7 hours after delivery. Cortisol concentration increased in SPON and PG cows, peaked 15 minutes after delivery (P < 0.001) but was higher in SPON versus PG cows (P < 0.001) during and within 2 hours after calving. Heart rate peaked during the expulsive phase of labor and was higher in SPON than in PG cows (time × group P < 0.01). The standard deviation of beat-to-beat interval and RMSSD peaked at the end of the expulsive phase of labor (P < 0.001), indicating high vagal activity. Standard deviation of beat-to-beat interval (P < 0.01) and RMSSD (P < 0.05) were higher in SPON versus PG cows. Based on physiological stress parameters, calving is perceived as stressful but expulsion of the calf is associated with a transiently increased vagal tone which may enhance uterine contractility.

Increased cortisol release and transport stress do not influence semen quality and testosterone release in pony stallions

The use of breeding stallions for equestrian competitions requires that fertility is not negatively affected by competition or transport to the competition site. In this study, effects of cortisol release induced by road transport (600 km), adrenocorticotropic hormone (ACTH) administration (3 × 0.5 mg synthetic ACTH) and placebo treatment on semen quality and testosterone release were investigated in Shetland stallions (N = 13) using a crossover design. Saliva for cortisol and blood for testosterone analysis were collected for 10 weeks after treatments. Semen was collected daily for 5 days directly after treatments and twice weekly for another 9 weeks. Total sperm count, sperm morphology, motility, and membrane integrity were analyzed. We hypothesized that elevated cortisol decreases testosterone concentration and semen quality. Cortisol concentrations increased in response to transport and ACTH (P < 0.001) but not control treatments (peak concentration, transport: 7.6 ± 2.4, ACTH: 13.7 ± 1.5, control: 3.8 ± 0.9 ng/mL). No treatment effects on testosterone existed. Total sperm count decreased with daily semen collections in week 1 (P < 0.01) but did not differ between the treatments. The percentage of motile, progressively motile, membrane-intact, and morphologically defective spermatozoa did not change over time from Days 2 to 6, and there existed no differences between the treatments. In conclusion, road transport evoked a stress response which was mimicked by ACTH treatment. Both treatments had no effect on testosterone release and semen quality. Testicular function in stallions is apparently well protected against transiently elevated cortisol concentrations, and stallions can be transported over longer distances without negatively affecting their fertility.

Deciphering the cues from riders’ legs

Equestrian competitions require both physical activity and mental adaptation in horses. Cortisol, heart rate, and heart rate variability (HRV) are accepted stress parameters and, in this study, have been determined in horses (n = 13) participating in equestrian competitions for up to 3 consecutive days. Participation in competitions caused an increase in salivary cortisol concentrations (e.g., on day 1 from 1.0 ± 0.2 before to 2.2 ± 0.4 ng/mL after the competition, days 1 and 2: P < 0.001, day 3: P < 0.05) and an increase in heart rate (days 1 and 2: P < 0.001, day 3: P = 0.01). A consistent decrease in HRV occurred only in response to the final competition on day 3 (P < 0.01). When horses competing in dressage and show jumping were compared, cortisol release and HRV did not differ between groups, but after the competition, heart rate was lower in dressage than in show jumping horses (P < 0.05). Heart rate increased not only during the actual competition but already when horses were prepared in their stables (e.g., day 1: −60 minutes, 38.6 ± 2; −5 minutes, 77 ± 7; competition, 81 ± 10 beats per minute; P < 0.01). In conclusion, participation in equestrian competitions caused an increase in cortisol release and heart rate and a decrease in HRV variables. However, competitions were not a major stressor compared with other anthropogenic challenges such as transport, to which horses are exposed regularly.