Variation Of Plasma Cortisol Research Articles

The Lack of Light-Dark and Feeding-Fasting Cycles Alters Temporal Events in the Goldfish (Carassius auratus) Stress Axis.

Simple SummaryThe circadian system synchronizes physiology and behavior to predictable environmental variations (daily cycles in light, temperature, or food availability). To this purpose, animals possess endogenous oscillators that provide internal temporal signals, thanks to rhythmic clock gene expression. In mammals, disruption of circadian oscillators correlates to overactivation of the stress axis, but this connection is less well known in teleosts. This work aims to learn how the absence of two main external signals (light-dark cycle and feeding schedule) impacts the oscillators in the hypothalamus-pituitary-interrenal) axis of goldfish, studying rhythms in locomotor activity, circulating cortisol, and clock gene expression. The removal of environmental synchronizators caused an increase in basal cortisol levels, indicating stress. Constant darkness also overrode clock gene rhythms in the whole axis but did not impede food anticipatory activity. Feeding at random times disrupted the interrenal clock, but cortisol and activity rhythms remained, concluding that clock gene rhythms in the interrenal tissue are unnecessary for rhythmic cortisol release or diurnality. This work evidences how environmental conditions impact the HPI axis, affecting endocrine and circadian functioning, which need to be considered when progressing towards optimizing fish welfare.Vertebrates possess circadian clocks, driven by transcriptional–translational loops of clock genes, to orchestrate anticipatory physiological adaptations to cyclic environmental changes. This work aims to investigate how the absence of a light-dark cycle and a feeding schedule impacts the oscillators in the hypothalamus-pituitary-interrenal axis of goldfish. Fish were maintained under 12L:12D feeding at ZT 2; 12L:12D feeding at random times; and constant darkness feeding at ZT 2. After 30 days, fish were sampled to measure daily variations in plasma cortisol and clock gene expression in the hypothalamus-pituitary-interrenal (HPI) axis. Clock gene rhythms in the HPI were synchronic in the presence of a light-dark cycle but were lost in its absence, while in randomly fed fish, only the interrenal clock was disrupted. The highest cortisol levels were found in the randomly fed group, suggesting that uncertainty of food availability could be as stressful as the absence of a light-dark cycle. Cortisol daily rhythms seem to depend on central clocks, as a disruption in the adrenal clock did not impede rhythmic cortisol release, although it could sensitize the tissue to stress.

Time-Dependent Effects of Acute Handling on the Brain Monoamine System of the Salmonid Coregonus maraena.

The immediate stress response involves the activation of the monoaminergic neurotransmitter systems including serotonin, dopamine and noradrenaline in particular areas of the fish brain. We chose maraena whitefish as a stress-sensitive salmonid species to investigate the influence of acute and chronic handling on the neurochemistry of monoamines in the brain. Plasma cortisol was quantified to assess the activation of the stress axis. In addition, we analyzed the expression of 37 genes related to the monoamine system to identify genes that could be used as markers of neurophysiological stress effects. Brain neurochemistry responded to a single handling (1 min netting and chasing) with increased serotonergic activity 3 h post-challenge. This was accompanied by a modulated expression of monoaminergic receptor genes in the hindbrain and a significant increase of plasma cortisol. The initial response was compensated by an increased monoamine synthesis at 24 h post-challenge, combined with the modulated expression of serotonin-receptor genes and plasma cortisol concentrations returning to control levels. After 10 days of repeated handling (1 min per day), we detected a slightly increased noradrenaline synthesis and a down-regulated expression of dopamine-receptor genes without effect on plasma cortisol levels. In conclusion, the changes in serotonergic neurochemistry and selected gene-expression profiles, together with the initial plasma cortisol variation, indicate an acute response and a subsequent recovery phase with signs of habituation after 10 days of daily exposure to handling. Based on the basal expression patterns of particular genes and their significant regulation upon handling conditions, we suggest a group of genes as potential biomarkers that indicate handling stress on the brain monoamine systems.

SUN-221 Subclinical Alpha-1 Antitrypsin Deficiency Is Associated with Increased Free Cortisol Fraction in Plasma and Altered Glucocorticoid Delivery to Tissues

BackgroundCorticosteroid Binding Globulin (CBG) binds >85% of plasma cortisol and controls the circulating free cortisol pool. Proteolytic cleavage by neutrophil elastase is proposed to reduce CBG binding affinity and increase free cortisol availability to inflamed tissues. The CORtisol NETwork (CORNET) consortium found that genetic variation at a locus spanning SERPINA1 (encoding alpha-1 antitrypsin, A1AT, the endogenous inhibitor of neutrophil elastase) and SERPINA6 (CBG) contributes to morning total plasma cortisol variation. We hypothesised that A1AT deficiency increases CBG cleavage and hence free plasma cortisol, resulting in increased tissue cortisol delivery in adipose and in HPA axis negative feedback. We tested this in recall-by-genotype studies of people who are heterozygous for inactivating mutations in SERPINA1.Methods16 healthy carriers of one of the two most common A1AT-deficiency single nucleotide polymorphisms (rs17580 & rs28929474) and 16 age-, gender- and BMI-matched controls were recruited from the Generation Scotland Biobank. Participants underwent combined receptor antagonist stimulation of the HPA axis (‘CRASH’) testing using RU486 400mg and spironolactone 200mg, or placebo in a double blind randomised crossover design. Plasma free cortisol was measured by isotopic dilution and ultrafiltration, total cortisol by LC-MS/MS, total CBG by ELISA, CBG binding capacity by radioligand displacement assay, and ACTH by immunoassay. Serum A1AT was measured by ELISA. Tissue cortisol (LC-MS/MS) and expression of glucocorticoid dependent transcripts (qPCR) were measured in subcutaneous adipose samples collected by needle biopsy.ResultsSerum A1AT was confirmed lower in those with heterozygous mutations vs wild type controls (411.3 +/- 27.44 vs 565.1 +/- 23.38 mg/dL, p=0.0002). No measurable differences in total CBG or CBG binding capacity were observed. However, plasma free cortisol fraction was higher in those carrying A1AT mutations (16.13 +/- 0.2 vs 13.88 +/- 0.04 %, p<0.0001). Adipose cortisol concentrations were not significantly different but expression of glucocorticoid responsive genes e.g. PER1 was 54% higher (p=0.014) in A1AT-deficient subjects. Plasma cortisol was elevated during CRASH testing in both groups, with the increment versus placebo tending to be lower in A1AT-deficient subjects (82.5 +/- 6.7 vs 126.7 +/- 6.8 nM).ConclusionAlpha-1 antitrypsin mutation heterozygosity, common in the general population, is associated with higher free cortisol fraction, consistent with enhanced cleavage of CBG. This is associated with evidence of enhanced delivery of glucocorticoid to adipose tissues but reduced HPA negative feedback, suggesting tissue-specific control of cortisol delivery by CBG.

Serum but not salivary cortisol levels are influenced by daily glycemic oscillations in type 2 diabetes

Diurnal salivary and plasma cortisol variations are considered valid expression of circadian cortisol rhythmicity. The aim of this study was to assess the reliability of salivary and plasma cortisol evaluating if glycemia and glycemic oscillations may interfere with their concentration.Methods: Forty-seven type 2 diabetic patients and 31 controls were studied for glycemic profile and diurnal salivary and plasma cortisol variations on two contemporary samples taken at 08:00 a.m. and 11:00 p.m (Late Night, LN). Glucose variability was evaluated in diabetic patients by considering the standard deviation of blood glucose (BGSD) readings, by calculating the mean amplitude of glycemic excursions (MAGEs) and continuous overlapping net glycemic action (CONGA).Results: A significant correlation between LN serum cortisol and morning fasting glycemia (r = 0.78; p = 0.004) was observed in T2DM group but not in the control group (r = 0.09; p = 0.74). While LN serum cortisol significantly correlated with CONGA in diabetic patients (r = 0.50; p &lt; 0.001), LN salivary cortisol did not correlate with any indices of glucose variability. Moreover, a highly significant correlation between LN salivary and LN serum cortisol concentrations was found in control group (r = 0.80; p &lt; 0.001) but not in diabetic patients (r = 0.07; p = 0.62) .Conclusions: This study shows for the first time that late night salivary cortisol may give more information than late night plasma cortisol on the dynamic of adrenal function of type 2 diabetic patients, as it is not significantly influenced by glycemic variations.

Serum but not salivary cortisol levels are influenced by daily glycemic oscillations in type 2 diabetes.

Diurnal salivary and plasma cortisol variations are considered valid expression of circadian cortisol rhythmicity. The aim of this study was to assess the reliability of salivary and plasma cortisol and if glycemia and glycemic oscillations may interfere with their concentration. Forty-seven type 2 diabetic patients and 31 controls were studied for glycemic profile and diurnal salivary and plasma cortisol variations on two contemporary samples taken at 08:00 a.m.-11:00 p.m (Late Night, LN). Glucose variability was evaluated in diabetic patients by considering the standard deviation of blood glucose (BGSD) readings, by calculating the mean amplitude of glycemic excursions (MAGEs) and continuous overlapping net glycemic action (CONGA). A significant correlation between LN serum cortisol and morning fasting glycemia (r=0.78; p=0.004) was observed in T2DM group but not in the control group (r=0.09; p=0.74). While LN serum cortisol significantly correlated with CONGA in diabetic patients (r=0.50; p<0.001), LN salivary cortisol did not correlate with any indices of glucose variability. Moreover, a highly significant correlation between LN salivary and LN serum cortisol concentrations was found in control group (r=0.80; p<0.001) but not in diabetic patients (r=0.07; p=0.62). This study shows for the first time that LN salivary rather than plasma cortisol may give information on the dynamics of adrenal function of type 2 diabetic patients, as it is not significantly influenced by glycemic variations. However, our preliminary results need to be confirmed by further studies with more complete evaluations including many more patients.

The Postprandial Rise in Plasma Cortisol in Men Is Mediated by Macronutrient-Specific Stimulation of Adrenal and Extra-Adrenal Cortisol Production

Circadian variation is a fundamental characteristic of plasma glucocorticoids, with a postprandial rise in cortisol an important feature. The diurnal rhythm is presumed to reflect alterations in hypothalamic-pituitary-adrenal axis activity; however, cortisol is produced not only by the adrenal glands but also by regeneration from cortisone by the enzyme 11β-hydroxysteroid dehydrogenase type 1, mainly in liver and adipose tissue. We tested the contribution of peripheral cortisol regeneration to macronutrient-induced circadian variation of plasma cortisol in humans. This was a randomized, single-blinded, crossover study. The study was conducted at a hospital research facility. Eight normal-weight healthy men participated in the study. Subjects were given isocaloric energy isodense flavor-matched liquid meals composed of carbohydrate, protein, fat, or low-calorie placebo during infusion of the stable isotope tracer 9,11,12,12-[2H]4-cortisol. Plasma cortisol increased similarly after all macronutrient meals (by ∼90 nmol/L) compared with placebo. Carbohydrate stimulated adrenal secretion and extra-adrenal regeneration of cortisol to a similar degree. Protein and fat meals stimulated adrenal cortisol secretion to a greater degree than extra-adrenal cortisol regeneration. The increase in cortisol production by 11β-hydroxysteroid dehydrogenase type 1 was in proportion to the increase in insulin. The postprandial cortisol rise was not accounted for by decreased cortisol clearance. Food-induced circadian variation in plasma cortisol is mediated by adrenal secretion and extra-adrenal regeneration of cortisol. Given that the latter has the more potent effect on tissue cortisol concentrations and that effects on adrenal and extra-adrenal cortisol production are macronutrient specific, this novel mechanism may contribute to the physiological interplay between insulin and glucocorticoids and the contrasting effects of certain diets on postprandial metabolism.

Quantification and comparison of baseline cortisol levels between aqueous and plasma from healthy anesthetized hound dogs utilizing mass spectrometry

The purpose of this study is to quantify and compare the resting cortisol levels between aqueous (Aq) and plasma of anesthetized hound dogs utilizing mass spectrometry. Nine hound breed dogs weighing between 20.8 and 29.2 kg (x = 26.3 kg, SD ± 2.6 kg) were utilized from a previous project. All dogs underwent two anesthesia sessions to harvest Aq from each eye respectively. A paired blood sample was taken immediately after aqueous centesis. The Aq and plasma were analyzed for cortisol levels using mass spectrometry. Correlation of cortisol levels in dog serum and ocular fluid was determined with Sigma Stat using Pearson's correlation analysis. The level of significance for correlation analysis was set at P < 0.05. The plasma resting cortisol levels in the dog ranged from 3.59 to 89.35 nm (x = 31.68 nm, SD ± 28.53 nm), while the Aq cortisol levels ranged from 0.82 to 5.62 nm (x = 2.73 nm, SD ± 1.94 nm). The correlation of cortisol levels in Aq compared to plasma was significant (P = 0.008) with a correlation coefficient of r = 0.779. Based on these results, 61% (r = 0.779(2) ) of the variation in Aq cortisol levels is explained by the variations in plasma cortisol levels. This study identified significant levels of cortisol in the Aq of the canine eye and positively correlated them with plasma cortisol levels. The dog may offer a representative model for further studies to help clarify the overall role of cortisol in the anterior chamber.

Seasonal variations in plasma cortisol, testosterone, progesterone and leukocyte profiles in a wild population of tuco‐tucos

AbstractStudies addressing seasonal changes in hormone levels are important in order to understand the interplays between ecology and physiology. In this study, we evaluated seasonal variations in cortisol, testosterone, and progesterone plasma levels in males and females of the subterranean rodent Ctenomys talarum. For the case of females, we also aimed to evaluate their capacity to increase their plasma cortisol concentrations in response to capture and restraint during reproductive and non‐reproductive seasons. In addition, we registered concomitant seasonal variations in the neutrophil to lymphocyte ratio (N:L) aimed to discriminate between basal and stress‐induced seasonal changes in cortisol levels in both males and females. Both basal and stressed‐induced cortisol levels were significantly higher in reproductive than non‐reproductive females. For the case of males, cortisol levels were also higher during the reproductive season, though values were two‐ to threefold lower than in females. The N:L ratios attained low values, typical of unstressed animals, in both males and females, indicating that the animals were not facing acute or chronic stressors at the moment of their capture. Testosterone levels in males were significantly elevated in relation to other mammals reaching up to 486 ng mL−1, with significantly higher levels during the reproductive season (mean: 209.45 ± 177.76 ng mL−1) and a remarkable inter‐individual variation. On the other hand, progesterone levels in females captured during reproductive and non‐reproductive seasons were not significantly different. This study shows that seasonal modulation in testosterone and also in baseline and stress‐induced cortisol levels occurs in tuco‐tucos associated with reproduction.

The ability of lambs to form expectations and the emotional consequences of a discrepancy from their expectations

Appraisal theories developed in cognitive psychology are used here to attempt to better understand emotional experiences in animals. We investigated whether lambs are able to form expectations and whether their emotional responses are affected by situations discrepant from the expectations they may have formed. Forty-five female lambs were trained to obtain a small or a large amount of food reward by performing an operant task (introducing their muzzle into a hole). Then, half the lambs were shifted to the large or the small reward (i.e. positive or negative shift respectively), while the remaining half continued to get the same amount of reward. Thereafter, the lambs previously submitted to a reward change were shifted back to their initial amount of reward (i.e. successive shifts) while the lambs previously maintained on the same amount of reward were subjected to extinction (no reward, thus a negative shift). Behavior, cortisol levels and cardiac activity were analyzed, and the treatments were compared with ANOVAs for mixed models. When the amount of reward delivered was decreased, the lambs showed more locomotor activity and performed the operant task at a higher frequency but less efficiently, and there was a decrease in the parasympathetic influence on their cardiac activity. These responses were exacerbated when the negative shift followed a positive one. Similar responses were observed under extinction, and these responses were more pronounced when animals were trained with a large amount of reward before extinction. In response to a positive shift, we noticed a decrease in the frequency of the attempted operant task; this occurred only when the positive shift followed a negative one. Variations in plasma cortisol were not consistent with changes in the amount of reward. This study shows that lambs evaluate a reward according to their previous experience with that reward. They are able to form expectations, and a discrepancy from these expectations influences emotional responses, especially in the case of a negative shift. Given the appraisal criteria used by lambs and the matching emotions, we can assume that the emotional response to a negative shift expressed by lambs could reflect the despair caused by frustration.

Impact of the human circadian system, exercise, and their interaction on cardiovascular function

The risk of adverse cardiovascular events peaks in the morning (≈9:00 AM) with a secondary peak in the evening (≈8:00 PM) and a trough at night. This pattern is generally believed to be caused by the day/night distribution of behavioral triggers, but it is unknown whether the endogenous circadian system contributes to these daily fluctuations. Thus, we tested the hypotheses that the circadian system modulates autonomic, hemodynamic, and hemostatic risk markers at rest, and that behavioral stressors have different effects when they occur at different internal circadian phases. Twelve healthy adults were each studied in a 240-h forced desynchrony protocol in dim light while standardized rest and exercise periods were uniformly distributed across the circadian cycle. At rest, there were large circadian variations in plasma cortisol (peak-to-trough ≈85% of mean, peaking at a circadian phase corresponding to ≈9:00 AM) and in circulating catecholamines (epinephrine, ≈70%; norepinephrine, ≈35%, peaking during the biological day). At ≈8:00 PM, there was a circadian peak in blood pressure and a trough in cardiac vagal modulation. Sympathetic variables were consistently lowest and vagal markers highest during the biological night. We detected no simple circadian effect on hemostasis, although platelet aggregability had two peaks: at ≈noon and ≈11:00 PM. There was circadian modulation of the cardiovascular reactivity to exercise, with greatest vagal withdrawal at ≈9:00 AM and peaks in catecholamine reactivity at ≈9:00 AM and ≈9:00 PM. Thus, the circadian system modulates numerous cardiovascular risk markers at rest as well as their reactivity to exercise, with resultant profiles that could potentially contribute to the day/night pattern of adverse cardiovascular events.

Evidence of major genes affecting stress response in rainbow trout using Bayesian methods of complex segregation analysis1

As a first step toward the genetic mapping of QTL affecting stress response variation in rainbow trout, we performed complex segregation analyses (CSA) fitting mixed inheritance models of plasma cortisol by using Bayesian methods in large full-sib families of rainbow trout. To date, no studies have been conducted to determine the mode of inheritance of stress response as measured by plasma cortisol response when using a crowding stress paradigm and CSA in rainbow trout. The main objective of this study was to determine the mode of inheritance of plasma cortisol after a crowding stress. The results from fitting mixed inheritance models with Bayesian CSA suggest that 1 or more major genes with dominant cortisol-decreasing alleles and small additive genetic effects of a large number of independent genes likely underlie the genetic variation of plasma cortisol in the rainbow trout families evaluated. Plasma cortisol is genetically determined, with heritabilities of 0.22 to 0.39. Furthermore, a major gene with an additive effect of -42 ng/mL (approximately 1.0 genetic SD) is segregating in this rainbow trout broodstock population. These findings provide a basis for designing and executing genome-wide linkage studies to identify QTL for stress response in rainbow trout broodstock and markers for selective breeding.

Diurnal ACTH and plasma cortisol variations in healthy dogs and in those with pituitary-dependent Cushing’s syndrome before and after treatment with retinoic acid

Daytime variations in ACTH and plasma cortisol were studied in healthy dogs and in dogs with pituitary-dependent hypercortisolism (PDH), before and after treatment with retinoic acid. In control dogs ACTH showed a higher concentration at 8.00 AM and between 2.00 and 6.00 PM, with the lowest concentration registered at 10.00 AM ( p < 0.05 vs. 8.00 AM and 2.00 PM and p < 0.01 vs. 4.00 PM). Cortisol did not show significant differences. In dogs with PDH, ACTH was lower at 8.00 AM (ACTH: p < 0.01 vs. 2.00 and 4.00 PM; and p < 0.05 vs. 6.00 PM). The lowest cortisol concentration was registered at 8.00 AM and 8.00 PM and the highest at 4.00 PM ( p < 0.05 vs. 8.00 AM and p < 0.01 vs. 8.00 PM). After treatment, the lowest ACTH concentration was registered at 10.00 AM ( p < 0.01 vs. 2.00 and 4.00 PM). To conclude, the adrenal is desensitized in PDH possibly showing negative in diagnostic tests.

Endocrine Disruption Induced by Organochlorines (OCs): Field Studies And Experimental Models

Long-range transport of persistent organic compounds by air and ocean currents from industrialized areas resulted in high levels of these pollutants in food webs in the Svalbard area. With the aim to test if organochlorine (OC) exposure in free-living polar bears from Svalbard affected their plasma steroid hormone concentrations, it was found that polychlorinated biphenyls (PCBs) were associated with increased progesterone levels in females. The sum of pesticides (∑pesticides) and ∑PCBs contributed significantly negative to the variation of the plasma testosterone in males, and the overall contribution of the OCs to the plasma cortisol variation was negative. A second objective was to study the effects of selected OCs (i.e., PCB 153 and PCB 126) on animal health as a consequence of effects on endocrine-regulated functions such as reproduction and immunity in a goat model focusing on long-term and low-level exposure during the periods of fetal development and in the neonatal period. Additionally, acute exposure was studied in adult mice. The results indicated that exposure to low doses of PCB 153 in utero and in the suckling period influenced reproductive functions and both PCB 153 and PCB 126 exerted immunomodulatory effects on the offspring, whereas acute exposure of adult mice had minor effects on male reproductive function.

Plasma cortisol variations in dairy cows after some usual or unusual manipulations

RiassuntoVariazioni del cortisolo ematico in bovine da latte a seguito di varie operazioni di stalla. Con lo scopo di meglio chiarire le interferenze sulla cortisolemia dovute alle tecniche di prelievo, alla manipolazione degli animali ed all’interazione uomo/bovina, sono state realizzate 4 prove per valutare l’effetto delle seguenti operazioni: prelievo ematico in bovine abituate o meno alla presenza umana, pulizia, mungitura, pesata e mascalcia. I valori basali di cortisolo hanno evidenziato l’usuale variabilità. Dopo 15 minuti dall’inizio delle operazioni la cortisolemia ha mostrato generalmente un picco. L’aumento è stato maggiore negli animali non avvezzi all’interazione con l’uomo ed in rapporto alla “invasività” delle operazioni; anche tra quelli assuefatti si è peraltro riscontrata una notevole variabilità della risposta. La valutazione della cortisolemia nella bovina da latte richiede grande cautela e una meticolosa standardizzazione metodologica.

Aberrant adrenal sensitivity to multiple ligands in unilateral incidentaloma with subclinical autonomous cortisol hypersecretion: a prospective clinical study.

Incidentally discovered adrenal tumours are frequently associated with subclinical autonomous cortisol hypersecretion of unknown origin. Aberrant hormone receptors have been observed in case reports of overt Cushing's syndrome. The question arises as to whether such receptors may be present in the functioning adrenal incidentaloma, which is common and might be a subclinical stage of Cushing's syndrome. Twenty-one consecutive patients with a unilateral incidentaloma, the biochemical features of subclinical cortisol hypersecretion and/or the scintigraphic features of an autonomously functioning adrenal adenoma were investigated for plasma cortisol responses to various stimuli: upright posture, meal, combined hypothalamic-hormones, the vasopressin analogue terlipressin, glucagon, angiotensin II, the serotonin 5-HT4 agonist cisapride, and ACTH. Six normal controls were similarly investigated. All subjects were studied during 8 mg per day dexamethasone in order to avoid any ACTH-dependent variation of plasma cortisol. The most constant responses in adrenal incidentalomas were observed after stimulation by terlipressin (18/20 patients, 28-415% cortisol increase) and cisapride (17/21 patients, 25-364% cortisol increase). Eighteen out of 21 patients responded to several stimuli (cortisol increase >or= 25%), and all responded to at least one stimulus other than ACTH, while such responses were absent in the controls. Plasma ACTH remained suppressed in all subjects throughout the study. Aberrant membrane receptors detected by in vivo stimulation tests appear to be common in autonomously functioning unilateral adrenocortical adenomas. These receptors may be involved in the modulation of cortisol secretion in adrenal incidentaloma, with potential therapeutic consequences for the control of subclinical cortisol hypersecretion.

Organochlorines Affect the Steroid Hormone Cortisol in Free-Ranging Polar Bears (Ursus maritimus) at Svalbard, Norway

Since the polar bear (Ursus maritimus) is among the most highly organochlorine-contaminated species of the Arctic mammals, there is growing concern that in addition to the natural stressors in the polar bear's environment, several organochlorines (OCs) may be able to change basic endocrine pathways. Alterations in the hypothalamic–pituitary–adrenal (HPA) axis may affect plasma cortisol concentrations and inhibit physiological processes involved in the maintenance of homeostasis in a way that may endanger the animal's health. Between 1995 and 1998, samples were collected from 121 male and 130 female free-ranging polar bears from the Svalbard area. The aim of the study was to investigate relationships between plasma cortisol concentrations, biological factors, and OCs. The variation in plasma cortisol concentrations was determined for the total sample. Axillary girth and body mass together with their interactions explained more than 50% of the variation in the plasma cortisol concentration. The sum of pesticides (Σpesticides) combined with the sum of polychlorinated biphenyls (ΣPCBs) and their interactions explained over 25% of the variation in the cortisol concentration. Although Σpesticides contributed negatively and ΣPCBs contributed positively to the variation in the plasma cortisol, the over-all contribution of the OCs to the plasma cortisol variation was negative. Despite the complexity on stress responses and the interactions with environmental factors, this study demonstrated that high concentrations of OCs in polar bears might alter plasma cortisol concentrations.

Cortisol dynamics following acute severe brain injury.

To study the diurnal rhythm of plasma cortisol and corticosteroid binding-globulin (CBG) in brain-injured patients managed in an intensive care unit (ICU). Observational clinical study. Twelve-bed medical/surgical critical care facility. Fifteen acute brain-injured (coma-inducing) patients: nine following trauma and six with subarachnoid haemorrhage (SAH). One morning and one evening blood sample were obtained from each patient via an existing arterial line at times which coincided with clinically indicated blood tests. The total cortisol measurements in this sample of brain-injured patients is similar to the normal reference range. Only two patients had morning total cortisol measurements greater than the reference range, 140-690 nmol/l, and five patients had evening measurements greater than the 80-330 nmol/l reference range. Eight patients demonstrated diurnal variation of plasma cortisol. Plasma CBG was significantly decreased in all 15 brain-injured patients. All patients had a free cortisol percentage greater than the quoted reference of 5% and five patients had measurements between 12-23%. No diurnal variation in CBG was detected. There was no association between age or mode of injury and cortisol secretion. Following acute severe brain injury, total serum cortisol is not elevated. This may indicate 'relative' hypocortisolaemia in relation to the clinically assessed stress. However, because of the decline in plasma CBG, plasma free cortisol is increased after acute severe brain injury.

Vegetable lipid sources for gilthead seabream ( Sparus aurata): effects on fish health

Commercial feeds for gilthead seabream are highly energetic, containing fish oil as the main lipid source. The steady production and raising prices of fish oil encourage the inclusion of vegetable oils in fish feeds. Fish oil could be at least partially substituted by vegetable oils in diets for marine species, being this substitution resulted in good feed utilization and maintenance of fish health, since imbalances in dietary fatty acids may alter the immunological status and stress resistance in fish. In order to evaluate the effect of vegetable oils on gilthead seabream health, fish were fed different isonitrogenous and isocaloric diets for 101 days (Experiment I) and 204 days (Experiment II). In Experiment I, diets were formulated to contain 60% of the fish oil used in the control diet (FO) as soybean oil (Diet 60SO), rapeseed oil (60RO), linseed oil (60LO) or a blend of those oils (Mix). In Experiment II, the same diets plus two which contained 80% of the fish oil as soybean oil (80SO) and linseed oil (80LO), respectively, were assayed. At the end of both experiments, basal levels of different immunological parameters were determined, including both humoral immunity (alternative complement pathway activity and serum lysozyme activity) and cellular immunity (circulating neutrophil activity and phagocytic index of head kidney macrophages). In addition, response to a confinement stress was assayed in terms of variations in plasma cortisol. The effect of dietary vegetable oils on fatty acid composition of head kidney macrophages and circulating red blood cells (RBC) was also studied. No effects of dietary vegetable oils were found in fish fed the experimental diets for a medium period. Feeding dietary vegetable oils for a long period did not affect lysozyme or neutrophil activity. However, in Experiment II, the inclusion of soybean oil reduced both serum alternative complement pathway activity (from 249 IU/ml (FO2) down to 153.8 IU/ml (60SO2)) and head kidney phagocytic activity (from 25.75% (FO2) down to 14.58% (80SO2). Inclusion of rapeseed oil reduced phagocytic activity. Fish fed vegetable oil-containing diets showed different patterns of stress response, especially those fish fed the linseed oil diets that showed a significant increase in plasma cortisol level after stress. The fatty acid composition of head kidney macrophages reflected the fatty acids content of the respective diets, but a selective incorporation of essential fatty acids into these cells was observed. The same trend was found in circulating red blood cells, indicating the important role of essential fatty acids on these cells. Sixty percent of fish oil can be replaced by a blend of different vegetable oils without affecting gilthead seabream health. However, if single vegetable oil is used to replace 60% of fish oil, fish health can be affected in terms of immunosuppression or stress resistance. Rapeseed oil affected head kidney macrophages activity, soybean oil affected serum alternative complement pathway activity and linseed oil altered stress response of fish.

Circadian rhythm characteristics of serum cortisol and dehydroepiandrosterone sulfate in healthy Chinese men aged 30 to 60 years. A cross-sectional study

The relation of adrenal function and aging has been the subject of intense interest in recent years. The circadian variations of plasma cortisol have been described in Caucasians, but little information is available on such hormone variations among the Chinese population, especially its changes with age. This study was, therefore, designed to examine the effects of age on the circadian variations of serum cortisol, dehydroepiandrosterone sulfate (DHEAS) and the molar ratio of cortisol/DHEAS in Chinese men, stratified by 10-year age-groups (i.e. men in their 30–60s, aged from 31 to 63 years old). Circadian variations of serum cortisol and DHEAS were documented at 2-h intervals from 8:00 to 22:00 and hourly from 22:00 to 8:00 in 26 healthy Chinese men. We found that the serum levels of both hormones showed a statistically significant circadian rhythmicity in all age-groups. The circadian pattern of serum cortisol was characterized by peaks (04:00–06:00) and troughs (18:00–24:00) occurring approximately 2 h earlier than those usually reported in Caucasians. Aging did not significantly influence serum cortisol concentrations, but serum DHEAS levels declined significantly with age: subjects in their 60s had significantly lower levels, and their cortisol/DHEAS molar ratios were significantly higher than those in the younger age-groups.

Timing of Initiation of the Preovulatory Luteinizing Hormone Surge and Its Relationship with the Circadian Cortisol Rhythm in the Human

The relationship between the hypothalamo-pituitary-gonadal (HPG) axis and the hypothalamo-pituitary-adrenal (HPA) axis has been well documented in the rat. In most cases, a negative coupling was observed and an inhibitory effect of the HPA axis upon the HPG was shown. In the female rat, a marked circadian rhythm of corticosterone plasma values is observed during each day of the estrous cycle, with maximal values around 08:00 p.m. The preovulatory luteinizing hormone (LH) surge also occurs at 08:00 p.m. on the day of proestrus. Here we measured circadian variations of plasma cortisol in humans in relation with the time of initiation of the preovulatory LH surge. Blood samples were taken at 08:00 a.m., 12:00 a.m., 04:00 p.m., 08:00 p.m., 12:00 p.m., and 04:00 a.m. from 19 subjects for 4 consecutive days, once 17β-estradiol (E₂) values reached 125 pg/ml (days 7–10 of the menstrual cycle). Serum E₂ and LH determinations were performed by microparticle enzyme immunoassays. Serum progesterone and plasma cortisol determinations were made using RIA methods. For plasma cortisol values, a marked circadian rhythm, with 2- to 3-fold higher values during the morning than during the afternoon, was almost identical before, during and after the LH surge. However, values were generally higher during the follicular phase than during the luteal phase. Maximum cortisol values occurred between 04:00 and 08:00 a.m. and minimal cortisol values between 04:00 and 08:00 p.m. Initiation of the LH surge (50% over the mean of previous values) occurred at 04:00 a.m. (20% of the cases) or at 08:00 a.m. (80% of the cases). There was a strong coupling between the onset of the surge and the acrophase of the cortisol circadian rhythm: maximal cortisol plasma values were seen at 04:00 a.m. when the LH preovulatory surge started at 04:00 a.m. and 08:00 a.m. when it started at 08:00 a.m. The present results show that the positive coupling documented in the female rat between the HPA and the HPG axis at the time of preovulatory LH surge is also present during the menstrual cycle in the human.