Adrenal Response Research Articles

Detection of Cortisol in Pbs Buffer and Fish Blood Plasma By Electrochemical Impedance Spectroscopy

Cortisol (MW = 362.5) is a steroid hormone produced in the human body by the adrenal gland in response to elevated levels of stress. Normal levels of cortisol in the human body range from 6-23 microgram per deciliter. Cortisol has also been widely studied in order to better understand fish physiology, with applications to fish ecology and fish farming, since cortisol levels can also be employed as a biomarker for reproductive activity. Following immobilization of the polyclonal antibody to cortisol atop an Au electrode, we have detected cortisol in both PBS buffer solution and fish blood plasma, with a detection range up to 0.5 microgram/ml. Binding of cortisol approximately follows the Langmuir adsorption isotherm, and the detection range is limited at high concentrations by saturation of the antibody film. This allows the use of sample dilution to reduce the physiological concentration of cortisol down to the range in which it can be detected by impedance biosensing. The advantage of this approach is that non-specific adsorption is also dramatically reduced by sample dilution. Non-specific adsorption in this system is unmeasurable, due to both the use of sample dilution and the use of BSA for surface blocking.

HDL is redundant for adrenal steroidogenesis in LDLR knockout mice with a human-like lipoprotein profile

The contribution of HDL to adrenal steroidogenesis appears to be different between mice and humans. In the current study, we tested the hypothesis that a difference in lipoprotein profile may be the underlying cause. Hereto, we determined the impact of HDL deficiency on the adrenal glucocorticoid output in genetically modified mice with a human-like lipoprotein profile. Genetic deletion of APOA1 in LDL receptor (LDLR) knockout mice was associated with HDL deficiency and a parallel increase in the level of cholesterol associated with nonHDL fractions. Despite a compensatory increase in the adrenal relative mRNA expression levels of the cholesterol synthesis gene, HMG-CoA reductase, adrenals from APOA1/LDLR double knockout mice were severely depleted of neutral lipids, as compared with those of control LDLR knockout mice. However, basal corticosterone levels and the adrenal glucocorticoid response to stress were not different between the two types of mice. In conclusion, we have shown that HDL is not critical for proper adrenal glucocorticoid function when mice are provided with a human-like lipoprotein profile. Our findings provide the first experimental evidence that APOB-containing lipoproteins may facilitate adrenal steroidogenesis, in an LDLR-independent manner, in vivo in mice.

Stress-induced oxytocin release and oxytocin cell number and size in prepubertal and adult male and female rats

Studies indicate that adolescent exposure to stress is a potent environmental factor that contributes to psychological and physiological disorders, though the mechanisms that mediate these dysfunctions are not well understood. Periadolescent animals display greater stress-induced hypothalamic–pituitary–adrenal (HPA) axis responses than adults, which may contribute to these vulnerabilities. In addition to the HPA axis, the hypothalamo-neurohypophyseal tract (HNT) is also activated in response to stress. In adults, stress activates this system resulting in secretion of oxytocin from neurons in the supraoptic (SON) and paraventricular (PVN) nuclei. However, it is currently unknown whether a similar or different response occurs in prepubertal animals. Given the influence of these hormones on a variety of emotional behaviors and physiological systems known to change as an animal transitions into adulthood, we investigated stress-induced HPA and HNT hormonal responses before and after stress, as well as the number and size of oxytocin-containing cells in the SON and PVN of prepubertal (30d) and adult (70d) male and female rats. Though we found the well-established protracted adrenocorticotropic hormone and corticosterone response in prepubertal males and females, only adult males and prepubertal females showed a significant stress-induced increase in plasma oxytocin levels. Moreover, though we found no pubertal changes in the number of oxytocin cells, we did find a pubertal-related increase in oxytocin somal size in both the SON and PVN of males and females. Taken together, these data indicate that neuroendocrine systems can show different patterns of stress reactivity before and after adolescent development and that these responses can be further modified by sex. Given the impact of these hormones on a variety of systems, it will be imperative to further explore these changes in hormonal stress reactivity and their role in adolescent health.

PSD-95 regulates CRFR1 localization, trafficking and β-arrestin2 recruitment

Corticotropin-releasing factor (CRF) is a neuropeptide commonly associated with the hypothalamic–pituitary adrenal axis stress response. Upon release, CRF activates two G protein-coupled receptors (GPCRs): CRF receptor 1 (CRFR1) and CRF receptor 2 (CRFR2). Although both receptors contribute to mood regulation, CRFR1 antagonists have demonstrated anxiolytic and antidepressant-like properties that may be exploited in the generation of new pharmacological interventions for mental illnesses. Previous studies have demonstrated CRFR1 capable of heterologously sensitizing serotonin 2A receptor (5-HT2AR) signaling: another GPCR implicated in psychiatric disease. Interestingly, this phenomenon was dependent on Postsynaptic density 95 (PSD-95)/Disc Large/Zona Occludens (PDZ) interactions on the distal carboxyl termini of both receptors. In the current study, we demonstrate that endogenous PSD-95 can be co-immunoprecipitated with CRFR1 from cortical brain homogenate, and this interaction appears to be primarily via the PDZ-binding motif. Additionally, PSD-95 colocalizes with CRFR1 within the dendritic projections of cultured mouse neurons in a PDZ-binding motif-dependent manner. In HEK 293 cells, PSD-95 overexpression inhibited CRFR1 endocytosis, whereas PSD-95 shRNA knockdown enhanced CRFR1 endocytosis. Although PSD-95 does not appear to play a significant role in CRF-mediated cAMP or ERK1/2 signaling, PSD-95 was demonstrated to suppress β-arrestin2 recruitment: providing a potential mechanism for PSD-95's inhibition of endocytosis. In revisiting previously documented heterologous sensitization, PSD-95 shRNA knockdown did not prevent CRFR1-mediated enhancement of 5-HT2AR signaling. In conclusion, we have identified and characterized a novel functional relationship between CRFR1 and PSD-95 that may have implications in the design of new treatment strategies for mental illness.

Overfeeding during a critical postnatal period exacerbates hypothalamic-pituitary-adrenal axis responses to immune challenge: a role for adrenal melanocortin 2 receptors.

Early life diet can critically program hypothalamic-pituitary-adrenal (HPA) axis function. We have previously shown rats that are overfed as neonates have exacerbated pro-inflammatory responses to immune challenge with lipopolysaccharide (LPS), in part by altering HPA axis responses, but how this occurs is unknown. Here we examined neonatal overfeeding-induced changes in gene expression in each step of the HPA axis. We saw no differences in glucocorticoid or mineralocorticoid receptor expression in key regions responsible for glucocorticoid negative feedback to the brain and no differences in expression of key HPA axis regulatory genes in the paraventricular nucleus of the hypothalamus or pituitary. On the other hand, expression of the adrenal melanocortin 2 receptor (MC2R) is elevated after LPS in control rats, but significantly less so in the neonatally overfed. The in vitro adrenal response to ACTH is also dampened in these rats, while the in vivo response to ACTH does not resolve as efficiently as it does in controls. These data suggest neonatal diet affects the efficiency of the adrenally-mediated response to LPS, potentially influencing how neonatally overfed rats combat bacterial infection.

Adrenocortical function in cane toads from different environments

The adrenocortical function of cane toads (Rhinella marina) exposed to different experimental procedures, as well as captured from different environments, was assessed by challenging the hypothalamic–pituitary–adrenal (HPA) axis. It was found that restriction stress as well as cannulation increased plasma corticosterone (B) levels for up to 12h. A single dose of dexamethasone (DEX 2mg/kg) significantly reduced B levels demonstrating its potential for use in the evaluation of the HPA axis in amphibia. We also demonstrate that 0.05IU/g BW (im) of synthetic adrenocorticotropic hormone (ACTH) significantly increased plasma B levels in cane toads. Changes in size area of the cortical cells were positively associated with total levels of B after ACTH administration. We also found differences in adrenal activity between populations. This was assessed by a DEX-ACTH test. The animals captured from the field and maintained in captivity for one year at the animal house (AH) present the highest levels of total and free B after ACTH administration. We also found that animals from the front line of dispersion in Western Australia (WA) present the weakest adrenal response to a DEX-ACTH test. The animals categorized as long established in Queensland Australia (QL), and native in Mexico (MX), do not shown a marked difference in the HPA activity. Finally we found that in response to ACTH administration, females reach significantly higher levels of plasma B than males. For the first time the adrenocortical response in cane toads exposed to different experimental procedures, as well as from different populations was assessed systematically.

Sex and stress steroids in adolescence: Gonadal regulation of the hypothalamic–pituitary–adrenal axis in the rat

This review provides an overview of the current understanding of the role of the hypothalamic–pituitary–gonadal (HPG) axis in regulating the hypothalamic–pituitary–adrenal (HPA) axis response to stressors. HPA function is influenced by both organizational (programming) and activational effects of gonadal hormones. Typically, in adult rats, estradiol increases and androgens decrease the HPA response to stressors, thereby contributing to sex differences in HPA function, and sensitivity of the HPA axis to gonadal steroids is in part determined by exposure to these hormones in early development. Although developmental differences in HPA function are well characterized, the extent to which gonadal steroids contribute to age differences in HPA function is not well understood. Deficits in the understanding of the relationships between the HPA and HPG axes are greatest for the adolescent period of development. The critical outstanding questions are, when do gonadal hormones begin to regulate HPA function in adolescence, and what mechanisms precipitate change in sensitivity of the HPA axis to the HPG axis at this stage of life.

Effect of Sleep Extension on the Subsequent Testosterone, Cortisol and Prolactin Responses to Total Sleep Deprivation and Recovery.

Total sleep deprivation (TSD) in humans is associated with altered hormonal levels, which may have clinical relevance. Less is known about the effect of an extended sleep period before TSD on these hormonal changes. Fourteen subjects participated in two experimental counterbalanced conditions (randomised cross-over design): extended sleep (21.00-07.00h time in bed, EXT) and habitual sleep (22.30-07.00h time in bed, HAB). For each condition, subjects performed two consecutive phases: six nights of either EXT or HAB. These nights were followed by 3days in the sleep laboratory with blood sampling at 07.00 and 17.00h at baseline (B-07.00 and B-17.00), after 24 and 34h of continuous awakening (24h-CA, 34h-CA) and after one night of recovery sleep (R-07.00 and R-17.00) to assess testosterone, cortisol, prolactin and catecholamines concentrations. At 24h of awakening, testosterone, cortisol and prolactin concentrations were significantly lower compared to B-07.00 and recovered basal levels after recovery sleep at R-07.00 (P<0.001 for all). However, no change was observed at 34h of awakening compared to B-17.00. No effect of sleep extension was observed on testosterone, cortisol and catecholamines concentrations at 24 and 34h of awakening. However, prolactin concentration was significantly lower in EXT at B-07.00 and R-07.00 compared to HAB (P<0.05, P<0.001, respectively). In conclusion, 24h of awakening inhibited gonadal and adrenal responses in healthy young subjects and this was not observed at 34h of awakening. Six nights of sleep extension is not sufficient to limit decreased concentrations of testosterone and cortisol at 24h of awakening but may have an impact on prolactin concentration.

MECHANISMS IN ENDOCRINOLOGY: New concepts to further unravel adrenal insufficiency during critical illness

The concept of 'relative' adrenal insufficiency during critical illness remains a highly debated disease entity. Several studies have addressed how to diagnose or treat this condition but have often yielded conflicting results, which further fuelled the controversy. The main reason for the controversy is the fact that the pathophysiology is not completely understood. Recently, new insights in the pathophysiology of the hypothalamic-pituitary-adrenal axis response to critical illness were generated. It was revealed that high circulating levels of cortisol during critical illness are explained more by reduced cortisol breakdown than by elevated cortisol production. Cortisol production rate during critical illness is less than doubled during the day but lower than in healthy subjects during the night. High plasma cortisol concentrations due to reduced breakdown in turn reduce plasma ACTH concentrations via feedback inhibition, which with time may lead to an understimulation and hereby a dysfunction of the adrenal cortex. This could explain the high incidence of adrenal insufficiency in the prolonged phase of critical illness. These novel insights have created a new framework for the diagnosis and treatment of adrenal failure during critical illness that has redirected future research.

A change in adrenal responsiveness in sotalol-treated patients with paroxysmal atrial fibrillation depending on autonomic nervous system tone

To evaluate the efficacy of sotalol depending on the magnitude of changes in adrenal responsiveness and autonomic nervous system tone in patients with paroxysmal atrial fibrillation (AF). Twenty-six patients with paroxysmal AF in the presence of coronary heart disease (CHD) and hypertension were examined. Sinus rhythm variability and sympathicotonic and vagotonic disorders were studied in patients with paroxysmal AF before and during sotalol treatment. A commercial Beta-ARM-Agat kit was used to estimate the adrenal responsiveness of erythrocyte membranes (β-APM), which can judge the body's individual sensitivity to β-adrenoblockers. Sotalol used in the average therapeutic doses of 160-240 mg did not reduce ejection fraction or increase atrioventricular conduction up to abnormal values. In patients with borderline and mild hypertension, the drug lowered blood pressure statistically significantly (p=0.01) and was well tolerated. The drug increased the sensitivity of β-adrenoblockers in patients with adrenergic AF. The effect of sotalol on the autonomic nervous system manifested in the higher power of a high-frequency spectral component of heart rate variability than in that of a low-frequency one. Long-term sotalol administration significantly reduced β-APM, increasing the sensitivity of adrenoceptors.

Assessment of ground transportation stress in juvenile Kemp's ridley sea turtles (Lepidochelys kempii).

Sea turtle rehabilitation centres frequently transport sea turtles for long distances to move animals between centres or to release them at beaches, yet there is little information on the possible effects of transportation-related stress ('transport stress') on sea turtles. To assess whether transport stress is a clinically relevant concern for endangered Kemp's ridley sea turtles (Lepidochelys kempii), we obtained pre-transport and post-transport plasma samples from 26 juvenile Kemp's ridley sea turtles that were transported for 13 h (n = 15 turtles) or 26 h (n = 11 turtles) by truck for release at beaches. To control for effects of handling, food restriction and time of day, the same turtles were also studied on 'control days' 2 weeks prior to transport, i.e. with two samples taken to mimic pre-transport and post-transport timing, but without transportation. Blood samples were analysed for nine clinical health measures (pH, pCO2, pO2, HCO3, sodium, potassium, ionized calcium, lactate and haematocrit) and four 'stress-associated' parameters (corticosterone, glucose, white blood cell count and heterophil-to-lymphocyte ratio). Vital signs (heart rate, respiratory rate and cloacal temperature) were also monitored. Corticosterone and glucose showed pronounced elevations due specifically to transportation; for corticosterone, this elevation was significant only for the longer transport duration, whereas glucose increased significantly after both transport durations. However, clinical health measures and vital signs showed minimal or no changes in response to any sampling event (with or without transport), and all turtles appeared to be in good clinical health after both transport durations. Thus, transportation elicits a mild, but detectable, adrenal stress response that is more pronounced during longer durations of transport; nonetheless, Kemp's ridley sea turtles can tolerate ground transportation of up to 26 h in good health. These results are likely to depend on specific transportation and handling protocols.

Endocrine responses to diverse stressors of capture, entanglement and stranding in leatherback turtles (Dermochelys coriacea).

Leatherback turtles (Dermochelys coriacea) are exposed to many anthropogenic stressors, yet almost no data on stress physiology exist for this species. As a first step toward understanding the physiological responses of leatherback turtles to stress, and with the particular goal of assessment of the effect of capture, we quantified corticosterone (an adrenal stress hormone) and thyroxine (a regulator of metabolic rate, often inhibited by chronic stress) in 17 healthy leatherback turtles captured at sea for scientific study, with comparisons to 15 'distressed' leatherbacks that were found entangled in fishing gear (n = 8), confined in a weir net (n = 1) or stranded on shore (n = 6). Distressed leatherbacks had significantly elevated corticosterone (mean ± SEM 10.05 ± 1.72 ng/ml, median 8.38 ng/ml) and free thyroxine (mean 0.86 ± 0.37 pg/ml, median 0.08 pg/ml) compared with healthy leatherbacks sampled immediately before release (after ∼40 min of handling; corticosterone, mean 4.97 ± 0.62 ng/ml, median 5.21 ng/ml; and free thyroxine, mean 0.05 ± 0.05 pg/ml, median 0.00 pg/ml). The elevated thyroxine in distressed turtles compared with healthy turtles might indicate an energetic burden of entanglement and stranding. Six of the healthy leatherbacks were sampled twice, at ∼25 and ∼50 min after the time of first disturbance. In all six individuals, corticosterone was higher in the later sample (earlier sample, mean 2.74 ± 0.88 ng/ml, median 2.61 ng/ml; later sample, mean 5.43 ± 1.29 ng/ml, median 5.38 ng/ml), indicating that capture and handling elicit an adrenal stress response in this species. However, the corticosterone elevation after capture appeared relatively mild compared with the corticosterone concentrations of the entangled and stranded turtles. The findings suggest that capture and handling using the protocols described (e.g. capture duration <1 h) might represent only a mild stressor, whereas entanglement and stranding might represent moderate to severe stressors.

Get the most out of blow hormones: validation of sampling materials, field storage and extraction techniques for whale respiratory vapour samples.

Studies are progressively showing that vital physiological data may be contained in the respiratory vapour (blow) of cetaceans. Nonetheless, fundamental methodological issues need to be addressed before hormone analysis of blow can become a reliable technique. In this study, we performed controlled experiments in a laboratory setting, using known doses of pure parent hormones, to validate several technical factors that may play a crucial role in hormone analyses. We evaluated the following factors: (i)practical field storage of samples on small boats during daylong trips; (ii)efficiency of hormone extraction methods; and (iii)assay interference of different sampler types (i.e. veil nylon, nitex nylon mesh and polystyrene dish). Sampling materials were dosed with mock blow samples of known mixed hormone concentrations (progesterone, 17β-estradiol, testosterone, cortisol, aldosterone and triiodothyronine), designed to mimic endocrine profiles characteristic of pregnant females, adult males, an adrenal glucocorticoid response or a zero-hormone control (distilled H2O). Results showed that storage of samples in a cooler on ice preserved hormone integrity for at least 6 h (P=0.18). All sampling materials and extraction methods yielded the correct relative patterns for all six hormones. However, veil and nitex mesh produced detectable assay interference (mean 0.22±0.04 and 0.18±0.03 ng/ml, respectively), possibly caused by some nylon-based component affecting antibody binding. Polystyrene dishes were the most efficacious sampler for accuracy and precision (P<0.001), but required an ethanol rinse for improved progesterone recovery (increased 81%; P<0.001). Awareness of assay interference from exogenous materials is crucial to future studies. This study establishes critical groundwork to help ensure that hormones can be measured accurately in samples obtained from field collections of whale blow.

Seasonal and sex differences in responsiveness to adrenocorticotropic hormone contribute to stress response plasticity in red-sided garter snakes (Thamnophis sirtalis parietalis).

As in many vertebrates, hormonal responses to stress vary seasonally in red-sided garter snakes (Thamnophis sirtalis parietalis). For example, males generally exhibit reduced glucocorticoid responses to a standard stressor during the spring mating season. We asked whether variation in adrenal sensitivity to adrenocorticotropic hormone (ACTH) explains why glucocorticoid responses to capture stress vary with sex, season and body condition in red-sided garter snakes. We measured glucocorticoids at 0, 1 and 4 h after injection with ACTH (0.1 IU g(-1)body mass) or vehicle in males and females during the spring mating season and autumn pre-hibernation period. Because elevated glucocorticoids can influence sex steroids, we also examined androgen and estradiol responses to ACTH. ACTH treatment increased glucocorticoids in both sexes and seasons. Spring-collected males had a smaller integrated glucocorticoid response to ACTH than autumn-collected males. The integrated glucocorticoid response to ACTH differed with sex during the spring, with males having a smaller glucocorticoid response than females. Although integrated glucocorticoid responses to ACTH did not vary with body condition, we observed an interaction among season, sex and body condition. In males, ACTH treatment did not alter androgen levels in either season, but androgen levels decreased during the sampling period. Similar to previous studies, plasma estradiol was low or undetectable during the spring and autumn, and therefore any effect of ACTH treatment on estradiol could not be determined. These data provide support for a mechanism that partly explains how the hypothalamus-pituitary-adrenal (HPA) axis integrates information about season, sex and body condition: namely, variation in adrenal responsiveness to ACTH.

Hypothalamic–pituitary–adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the TSST than do women during the follicular phase of the menstrual cycle.

Diminished adrenal sensitivity to endogenous and exogenous adrenocorticotropic hormone in critical illness: a prospective cohort study.

IntroductionAdrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase.MethodsWe prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests.ResultsPatients with low (<250 nM) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar.ConclusionsEven though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens.

Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied. Here, we propose a previously undescribed endocrine mechanism regulating female aggression via direct action of the pineal hormone melatonin on adrenal androgens. We examined this in a solitary hamster species, Phodopus sungorus, in which both sexes are highly territorial across the seasons, and display increased aggression concomitant with decreased serum levels of sex steroids in short 'winter-like' days. Short- but not long-day females had increased adrenal DHEA responsiveness co-occurring with morphological changes in the adrenal gland. Further, serum DHEA and total adrenal DHEA content were elevated in short days. Lastly, melatonin increased DHEA and aggression and stimulated DHEA release from cultured adrenals. Collectively, these findings demonstrate that DHEA is a key peripheral regulator of aggression and that melatonin coordinates a 'seasonal switch' from gonadal to adrenal regulation of aggression by direct action on the adrenal glands.

Predator—prey interaction between individuals: 2. Mechanisms of selection

Predator–prey interactions were studied in natural experiments (windhounds pursuing wild saiga antelopes and brown hares in native landscapes). A lower pursuit success compared to that of wild predators was found. The prey of windhounds was represented by animals not only with various abnormalities in the internal organs and impaired conditions (see Communication 1), but also with an increased amount of microflora on the tested body surface fragments. Possible mechanisms of distant discrimination between the accessible and inaccessible objects of hunt that ensure the high selectivity of prey elimination are analyzed. Published and experimental data demonstrating the regulation of the amount of microflora by the physiological state of macroorganisms with different well-being levels are presented. Changes in the microflora are a consequence, but not the cause, of the reduced adaptation of the organism. The causes of such reduction are different, but their result is the development of the adrenal response, which modulates, in particular, the entire microbiota of the macroorganism. The transformation of the microbiota underlies the changes in the odour of potentially available prey, thus providing to predator the possibility of distant evaluation of the perspectives for pursuit and selection of prey by its fitness.

A Prospective Multicenter Study Evaluating Secondary Adrenal Suppression After Antiemetic Dexamethasone Therapy in Cancer Patients Receiving Chemotherapy: A Korean South West Oncology Group Study

In a previous pilot study, adrenal suppression was found to be common after antiemetic dexamethasone therapy in cancer patients. The objective of this large prospective multicenter study was to confirm the incidence and factors associated with secondary adrenal suppression related to antiemetic dexamethasone therapy in cancer patients receiving chemotherapy. Chemotherapy-naïve patients who were scheduled to receive at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Patients with a suppressed adrenal response before chemotherapy or those administered corticosteroids within 6 months of enrollment in the study were excluded. Between October 2010 and August 2014, 481 patients receiving chemotherapy underwent the rapid adrenocorticotropic hormone (ACTH) stimulation test to assess eligibility; 350 of these patients were included in the final analysis. Fifty-six patients (16.0%) showed a suppressed adrenal response in the rapid ACTH stimulation test at 3 or 6 months after the start of the first chemotherapy. The incidence of adrenal suppression was affected by age, performance status, stage, and use of megestrol acetate in univariate analysis. Multivariate analysis revealed that secondary adrenal suppression associated with antiemetic dexamethasone therapy was significantly associated with megestrol acetate treatment (odds ratio: 3.06; 95% confidence interval: 1.60 to 5.86; p < .001). This large prospective study indicates that approximately 15% of cancer patients receiving chemotherapy with a normal adrenal response show suppressed adrenal responses after antiemetic dexamethasone therapy. This result was particularly significant for patients cotreated with megestrol acetate.

Involvement of the TORC isoforms in adrenal responsiveness to basal and stress-induced HPA activity

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