Mercury toxicity risk and corticosterone levels across the breeding range of the Yellow-breasted Chat

Mercury (Hg) is an environmental contaminant that can negatively impact human and wildlife health. For songbirds, Hg risk may be elevated near riparian habitats due to the transfer of methylmercury (MeHg) from aquatic to terrestrial food webs. We measured Hg levels in tail feathers sampled across the breeding range of the Yellow-breasted Chat (Icteria virens), a riparian songbird species of conservation concern. We assessed the risk of Hg toxicity based on published benchmarks. Simultaneously, we measured corticosterone, a hormone implicated in the stress response system, released via the hypothalamus-pituitary-adrenal axis. To better understand range-wide trends in Hg and corticosterone, we examined whether age, sex, subspecies, or range position were important predictors. Lastly, we examined whether Hg and corticosterone were correlated. Hg levels in chats were relatively low: 0.30 ± 0.02 µg/g dry weight. 148 out of 150 (98.6%) had Hg levels considered background, and 2 (1.6%) had levels considered low toxicity risk. Hg levels were similar between sexes and subspecies. Younger chats (<1 year) had higher Hg levels than older chats (>1 year). Hg levels were lowest in the northern and central portion of the eastern subspecies’ range. Corticosterone concentrations in feathers averaged 3.68 ± 0.23 pg/mm. Corticosterone levels were similar between ages and sexes. Western chats had higher levels of corticosterone than eastern chats. Hg and corticosterone were not correlated, suggesting these low Hg burdens did not affect the activity of the hypothalamus-pituitary-adrenal axis. Altogether, the chat has low Hg toxicity risk across its breeding range, despite living in riparian habitats.

Altered Cortisol Metabolism Increases Nocturnal Cortisol Bioavailability in Prepubertal Children With Type 1 Diabetes Mellitus

ObjectiveDisturbances in the activity of the hypothalamus-pituitary-adrenal axis could lead to functional alterations in the brain of diabetes patients. In a later perspective of investigating the link between the activity of the hypothalamus-pituitary-adrenal axis and the developing brain in children with diabetes, we assessed here nocturnal cortisol metabolism in prepubertal children with type 1 diabetes mellitus (T1DM).MethodsPrepubertal patients (aged 6–12 years) diagnosed with T1DM at least 1 year previously were recruited, along with matched controls. Nocturnal urine samples were collected, with saliva samples taken at awakening and 30 minutes after awakening. All samples were collected at home over 5 consecutive days with no detectable nocturnal hypoglycaemia. The State-Trait Anxiety Inventory (trait scale only) and Child Depression Inventory were also completed. Glucocorticoid metabolites in the urine, salivary cortisol (sF) and cortisone (sE) were measured by liquid chromatography–tandem mass spectrometry. Metabolic data were analysed by logistic regression, adjusting for sex, age, BMI and trait anxiety score.ResultsUrine glucocorticoid metabolites were significantly lower in T1DM patients compared to controls. 11β-hydroxysteroid dehydrogenase type 1 activity was significantly higher, while 11β-hydroxysteroid dehydrogenase type 2, 5(α+β)-reductase and 5α-reductase levels were all lower, in T1DM patients compared to controls. There was a significant group difference in delta sE level but not in delta sF level between the time of awakening and 30 minutes thereafter.ConclusionsOur findings suggest that altered nocturnal cortisol metabolism and morning HPA axis hyperactivity in children with T1DM leads to greater cortisol bioavailability and lower cortisol production as a compensatory effect. This altered nocturnal glucocorticoid metabolism when cortisol production is physiologically reduced and this HPA axis hyperactivity question their impact on brain functioning.

QT Interval Instability and Variability in Dogs with Hyperadrenocorticism

Hyperadrenocorticism is one of the most common endocrine diseases in dogs. In humans, it is clearly associated with a higher risk of cardiovascular events, but studies in dogs are scarce. To investigate the arrhythmogenic risk of dogs with hyperadrenocorticism, indices of variability and instability of the QT interval were studied in 38 dogs with hyperadrenocorticism and in 12 healthy dogs: variance (QTv), total instability (TI), short-term (STI) and long-term (LTI), and mean (QTm). Except for QTm, all parameters studied were higher in the hyperadrenocorticism group than in the control group. In addition, STI and QTv showed moderate positive correlation with left ventricle wall thickness. To a better understanding on the effect of the hypothalamus-pituitary-adrenal axis on ventricular repolarization, the hyperadrenocorticism group was subdivided according to the percentage of variation in plasma cortisol concentration (<30.1%; 30.1-60%; >60%) 8 hours after low-dose administration of dexamethasone. There was statistical difference in QTv, TI and LTI indices between the control group and the <30.1% and >60% groups, and in STI index between the control group and the >60% group. There was no statistical difference between sex groups in any of the electrocardiographic parameters studied. This result may indicate that the etiology of hyperadrenocorticism, and its consequent influence on hypothalamus-pituitary-adrenal axis could interfere on the heterogeneity of ventricular repolarization parameters in different ways, especially in the short-term stability; however further studies are necessary to understand the role of cortisol on electrical instability in dogs.

Stress and spirituality in relation to HPA axis gene methylation among US Black women: results from the Black Women's Health Study and the Study on Stress, Spirituality and Health

Background: Few epigenetics studies have been conducted within the Black community to examine the impact of diverse psychosocial stressors and resources for resiliency on the stress pathway (hypothalamus-pituitary-adrenal axis). Methods: Among 1000 participants from the Black Women's Health Study, associations between ten psychosocial stressors and DNA methylation (DNAm) of four stress-related genes ( NR3C1, HSDB1, HSD11B2 and FKBP5) were tested. Whether religiosity or spirituality (R/S) significantly modified these stress-DNAm associations was also assessed. Results: Associations were found for several stressors with DNAm of individual CpG loci and average DNAm levels across each gene, but no associations remained significant after false discovery rate (FDR) correction. Several R/S variables appeared to modify the relationship between two stressors and DNAm, but no identified interaction remained significant after FDR correction. Conclusion: There is limited evidence for a strong signal between stress and DNAm of hypothalamus-pituitary-adrenal axis genes in this general population cohort of US Black women.

Contribution of Growth Arrest-Specific 5/miR-674 to the Hypothalamus Pituitary Adrenal Axis Regulation Effect by Electroacupuncture following Trauma

<b><i>Background:</i></b> Electroacupuncture (EA) can improve trauma-induced hypothalamus pituitary adrenal axis (HPA) hyperactivity. However, the mechanism underlying the EA effect has not been fully understood. <b><i>Methods and Study Design:</i></b> This study was undertaken to explore the role of hypothalamic growth arrest-specific 5 (Gas5) in the regulation of EA on HPA axis function post-surgery. Paraventricular nuclear Gas5 levels were upregulated in rats using an intracerebroventricular injection of pAAV-Gas5. Primary hypothalamic neurons and 293T cells were cultured for miRNA and siRNAs detection. Radioimmunoassay, PCR, Western blot, and immunohistochemistry were used for HPA axis function evaluation. <b><i>Results:</i></b> The overexpression of Gas5 abolished the effect of EA on the regulation of trauma-induced HPA axis hyperactivity. Using a bioinformatics analysis and dual luciferase assay, we determined that miRNA-674 was a target of Gas5. Additionally, miRNA-674 levels were found to have decreased in trauma rats, and this effect was reversed after EA intervention. TargetScan analysis showed that serum and glucocorticoid inducible kinase 1 (SGK1) were targets of miR-674. Moreover, we found that SGK1 protein levels increased in trauma rats and SGK1 expression inhibition alleviated HPA axis abnormality post-surgery. EA could improve the number of hypothalamus iba-1 positive cells and hypothalamic interleukin 1 beta protein expression. <b><i>Conclusions:</i></b> Our study demonstrated the involvement of the hypothalamic Gas5/miRNA-674/SGK1 signaling pathway in EA regulation of HPA axis function after trauma.

Effects of hydrocortisone and yohimbine on selective attention to emotional cues

Introduction: Facial expressions contain important affective information, and selective attention to facial expression provides an advantage in the face of loss, stress and danger. In addition, the sympathetic nervous system and hypothalamus-pituitary-adrenal axis mediate the organism’s response to loss and danger. Here, we aimed at investigating the influence of sympathetic nervous system and hypothalamus-pituitary-adrenal axis activation on selective attention to affective facial stimuli. Methods and materials: One hundred-and-four healthy men between 18–35 years old (mean (standard deviation) age: 24.1 (3.5) years) participated in the study. We used a randomised, double-blind, placebo-controlled design. Participants received either: (a) yohimbine, (b) hydrocortisone, (c) yohimbine and hydrocortisone or (d) placebo only and participated in a dot-probe task with sad, happy and neutral faces. We collected salivary samples to measure cortisol and alpha amylase activity in addition to measurements of blood pressure and heart rate. Salivary cortisol served as correlate of hypothalamus-pituitary-adrenal axis activation and salivary alpha amylase activity, blood pressure and heart rate as correlates of sympathetic nervous system activation. Measurements were carried out before and after drug administration. Results: We did not find a main effect or interaction effect of hydrocortisone or yohimbine administration on selective attention to happy faces. However, we found an interaction of yohimbine and hydrocortisone on selective attention to sad faces. Post-hoc t-test revealed an attentional bias away from sad stimuli and towards neutral faces in the hydrocortisone-only group. Discussion: Only hydrocortisone administration led to an attentional bias away from sad faces. Future studies should investigate these effects in major depression disorder, as this disorder is characterised by glucocorticoid resistance and increased processing of sad stimuli.

Immune and endocrine systems

In this chapter, the placebo effect in the immune and endocrine system is described, where learning, mainly Pavlovian conditioning, is the basic mechanism. Conditioned immunosuppression affects a number of immune mediators, like interleukin-2 and interferon-gamma (IFN-γ‎). Nocebo effects may occur in the immune system; indeed, some negative allergic reactions may be induced by the administration of nocebos. Some mechanisms in the endocrine system are also described. In fact, the responses of some hormones, like insulin, growth hormone, and cortisol, have been successfully obtained by means of a conditioning procedure. In addition, the hypothalamus–pituitary–adrenal axis may represent an important system in placebo and nocebo responsiveness in the endocrine system.

Chronic stress, epigenetics, and adipose tissue metabolism in the obese state

In obesity, endocrine and metabolic perturbations, including those induced by chronic activation of the hypothalamus–pituitary–adrenal axis, are associated with the accumulation of adipose tissue and inflammation. Such changes are attributable to a combination of genetic and epigenetic factors that are influenced by the environment and exacerbated by chronic activation of the hypothalamus–pituitary–adrenal axis. Stress exposure at different life stages can alter adipose tissue metabolism directly through epigenetic modification or indirectly through the manipulation of hypothalamic appetite regulation, and thereby contribute to endocrine changes that further disrupt whole-body energy balance. This review synthesizes current knowledge, with an emphasis on human clinical trials, to describe metabolic changes in adipose tissue and associated endocrine, genetic and epigenetic changes in the obese state. In particular, we discuss epigenetic changes induced by stress exposure and their contribution to appetite and adipocyte dysfunction, which collectively promote the pathogenesis of obesity. Such knowledge is critical for providing future directions of metabolism research and targets for treating metabolic disorders.