Circulating Cortisol Concentrations Research Articles

Impact of Delta SARS-CoV-2 Infection on Glucose Metabolism: Insights on Host Metabolism and Virus Crosstalk in a Feline Model.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes enhanced mortality in people with metabolic and cardiovascular diseases. Other highly infectious RNA viruses have demonstrated dependence on glucose transport and utilization, so we hypothesized that SARS-CoV-2 infection could lead to alterations in cellular and whole-body glucose metabolism. Twenty-four healthy domestic cats were intratracheally inoculated with B.1.617.2 (delta) SARS-CoV-2 and samples were collected at 4- and 12-days post-inoculation (dpi). Blood glucose and circulating cortisol concentrations were elevated at 4 and 12 dpi. Serum insulin concentration was statistically significantly decreased, while angiotensin 2 concentration was elevated at 12 dpi. SARS-CoV-2 RNA was detected in the pancreas and skeletal muscle at low levels; however, no change in the number of insulin-producing cells or proinflammatory cytokines was observed in the pancreas of infected cats through 12 dpi. SARS-CoV-2 infection statistically significantly increased GLUT protein expression in both the heart and lungs, correlating with increased AMPK expression. In brief, SARS-CoV-2 increased blood glucose concentration and cardio-pulmonary GLUT expression through an AMPK-dependent mechanism, without affecting the pancreas, suggesting that SARS-CoV-2 induces the reprogramming of host glucose metabolism. A better understanding of host cell metabolism and virus crosstalk could lead to the discovery of novel metabolic therapeutic targets for patients affected by COVID-19.

Exploring transcriptional and post-transcriptional epigenetic regulation of crf and 11βhsd2 in rainbow trout brain during chronic social stress

Using dominance hierarchies in juvenile rainbow trout (Oncorhynchus mykiss) as a model of chronic social stress in fish, we explored whether epigenetic transcriptional and post-transcriptional mechanisms are involved in the gene expression of corticotropin-releasing factor (crf) and 11β-hydroxysteroid dehydrogenase (11βhsd2), key factors involved in the regulation of the endocrine stress axis response. In juvenile rainbow trout pairs, subordinate individuals display sustained elevation of circulating cortisol concentrations. Cortisol production is controlled by the hypothalamic-pituitary-interrenal (HPI) axis in fish and initiated by CRF release from the preoptic area (POA). Given that crf is modulated during chronic social stress, and that such stress has been implicated in the epigenetic regulation of crf in other taxa, we probed a role for epigenetic regulation of crf transcript abundance in chronically stressed rainbow trout. We also investigated the regulation of the cortisol-metabolising enzyme 11βhsd2 in the POA, which is upregulated in subordinates. The potential involvement of DNA methylation and microRNAs (miRNAs) in the regulation of crf transcript abundance was investigated during social stress in the POA of fish, as was the potential involvement of miRNAs in 11βhsd2 regulation. Although transcript abundances of crf were elevated in subordinate fish after 4 days, DNA methylation profiles within putative promoter sequences upstream of the crf gene were not significantly affected by chronic stress. An inverse relationship between crf and its predicted posttranscriptional regulator miR-103a-3p in the POA suggests that miRNAs may be involved in mediating the effects of chronic social stress on key components of the endocrine stress axis.

SAT040 Administration Of A DHCR24 Inhibitor Reduces The Excessive Adrenal Steroidogenesis In db/db Mice Through Effects The Alteration Of Intracellular Cholesterol Metabolism

Abstract Disclosure: R. Kamigaki: None. H. Kameda: None. Y. Shibayama: None. H. Nomoto: None. K. Cho: None. A. Nakamura: None. S. Jin: None. K. Matoba: None. H. Miyoshi: None. T. Atsumi: None. Background and purpose: The circulating cortisol concentrations of patients with type 2 diabetes are high, suggesting that cortisol may be involved in diabetic complications. It has also been reported that the db/db mouse, a model of obesity and type 2 diabetes, has high circulating concentrations of steroid hormones. However, the mechanisms involved are unclear. In our previous study, we found that the expression of DHCR24, an enzyme that converts desmosterol (DES) to cholesterol (Chol) as part of de novo cholesterol synthesis, is upregulated in the adrenal glands of db/db mice. In the present study, we aimed to determine the effects of a DHCR24 inhibitor on adrenal steroidogenesis in db/db mice. Methods: Eight-week-old male db/db and db/+ mice were allocated to two groups, which were administered a weekly intraperitoneal injection of a DHCR24 inhibitor (U18666A; 10 mg/kg; (U) or PBS (P). Blood samples and their adrenal glands were collected 4 weeks later. We then compared the blood glucose, body mass, adrenal DES content, adrenal Chol content, and serum corticosterone (B) between the two groups. Sterols were extracted from adrenal tissue using the Folch method, and their concentrations were measured following picolinyl derivatization using liquid chromatography tandem-mass spectrometry. Results: There were no significant differences in the blood glucose concentrations or body masses of the P and U groups of both db/+ and db/db mice. The adrenal DES/adrenal mass ratio was higher in the db/db U group than in the db/db P group (db/db P vs. db/db U vs. db/+ P vs. db/+ U: 16.0±4.3 vs. 98.4±73.2 vs. 42.9±8.6 vs. 124.9±64.6 ng/mg, respectively; p<0.05). The adrenal Chol/adrenal mass and serum B concentration were lower in the db/db U and db/+ P groups than in the db/db P group (db/db P vs. db/db U vs. db/+ P vs. db/+ U: 2.1±0.2 vs. 1.3±0.2 vs. 1.1±0.6 vs. 1.3±0.2 μg/mg; and 232.8±20.1 vs. 189.6±13.1 vs. 126.3±20.6 vs. 111.2±25.8 ng/mL; respectively; all p<0.05). Conclusion: DHCR24 inhibition reduces cholesterol production and steroid hormone synthesis in the adrenal glands of db/db mice. This implies that the abnormal adrenal cholesterol metabolism in db/db mice plays a role in the greater adrenal steroidogenesis in type 2 diabetes, and that adrenal cholesterol metabolism may represent a novel therapeutic target for the affected patients. Presentation: Saturday, June 17, 2023

Hair Cortisol Concentrations in Feral Horses and the Influence of Physiological and Social Factors

Cortisol is a glucocorticoid hormone produced during activation of the hypothalamic–pituitary–adrenal axis (HPA) in response to psychological or physiological demands. High amounts of circulating cortisol can be found in individuals experiencing energetically demanding physiological events, such as pregnancy, lactation, injury, or starvation, but, also, in individuals who may have less obvious HPA activation from social situations. The feral horse population on Sable Island (Nova Scotia, Canada) provides an opportunity to look at hair cortisol concentration (HCC) as a proxy for circulating cortisol concentration to better understand physiological correlates. The horse’s complex social structure also allows us to look at how the population and group structure may influence HPA activation. Hair samples (n = 282) were analyzed from 113 females and 135 males. Females with dependent offspring (foals) had higher HCC than those females without dependent offspring (p = 0.005). Horses in poor body condition were also more likely to have higher HCC (females: p < 0.001, males: p = 0.028); females had greater variation in the body condition index (BCI), which also correlated with foal production. In general, the top-ranked models describing female cortisol levels included age, BCI, presence of a foal, as well as social measures such as harem size and the number of bachelors in the vicinity. The top model describing male cortisol levels included age, BCI, and year of collection only, and the number of bachelors in the home range appeared in subsequent, though still high-ranked, models. Among the variables not of direct interest, we found some significant results relating to hair color and hair texture. Differences in HCC patterns between feral and domestically kept horses (e.g., age and sex) are likely linked to periods of resource limitations, particularly for individuals experiencing energetically demanding processes such as reproduction, illness/parasitism, or related to experiencing the full range of social and reproductive behaviors.

Large and in charge: cortisol levels vary with sex, diet, and body mass in an Antarctic predator, the leopard seal

Evaluating physiological responses in the context of a species’ life history, demographics, and ecology is essential to understanding the health of individuals and populations. Here, we measured the main mammalian glucocorticoid, cortisol, in an elusive Antarctic apex predator, the leopard seal (Hydrurga leptonyx). We also examined intraspecific variation in cortisol based on life history (sex), morphometrics (body mass, body condition), and ecological traits (δ15N, δ13C). To do this, blood samples, life history traits, and morphometric data were collected from 19 individual leopard seals off the Western Antarctic Peninsula. We found that adult leopard seals have remarkably high cortisol concentrations (100.35 ± 16.72 μg/dL), showing the highest circulating cortisol concentration ever reported for a pinniped: 147 μg/dL in an adult male. Leopard seal cortisol concentrations varied with sex, body mass, and diet. Large adult females had significantly lower cortisol (94.49 ± 10.12 μg/dL) than adult males (120.85 ± 6.20 μg/dL). Similarly, leopard seals with higher isotope values (i.e., adult females, δ15N: 11.35 ± 0.69‰) had lower cortisol concentrations than seals with lower isotope values (i.e., adult males, δ15N: 10.14 ± 1.65‰). Furthermore, we compared cortisol concentrations across 26 closely related Arctoid taxa (i.e., mustelids, bears, and pinnipeds) with comparable data. Leopard seals had the highest mean cortisol concentrations that were 1.25 to 50 times higher than other Arctoids. More broadly, Antarctic ice seals (Lobodontini: leopard seal, Ross seal, Weddell seal, crabeater seal) had higher cortisol concentrations compared to other pinnipeds and Arctoid species. Therefore, high cortisol is a characteristic of all lobodontines and may be a specialized adaptation within this Antarctic-dwelling clade. Together, our results highlight exceptionally high cortisol concentrations in leopard seals (and across lobodontines) and reveal high variability in cortisol concentrations among individuals from a single location. This information provides the context for understanding how leopard seal physiology changes with life history, ecology, and morphology and sets the foundation for assessing their physiology in the context of a rapidly changing Antarctic environment.

Residential greenness and hair cortisol levels during the first trimester of pregnancy

Background and aimStudies have shown that increased maternal cortisol level is associated with child adverse health outcomes. Hair cortisol (HC) is suitable for assessing long-term circulating cortisol concentration. Only two previous studies reported beneficial associations between cortisol and residential greenness during pregnancy and no study focused on the first trimester. Our aim was to evaluate the association between residential greenness and first trimester HC levels among pregnant women in Israel. MethodsWomen were recruited during second and third trimesters. Hair samples were collected from the scalp and retrospective HC levels during the first trimester were quantified for 217 women. HC levels were natural log transformed and outliers were excluded. Based on geocoded birth address, small area sociodemographic status (SES) and mean residential surrounding greenness were calculated using high-resolution satellite-based Normalised Difference Vegetation Index (NDVI) data at 100, 300 and 500-m buffers in a cross-sectional approach. In addition, longitudinal exposure to mean greenness during a week preconception and during the first trimester were calculated. Missing covariates were imputed and linearity of the associations were evaluated. Generalized linear models were used to estimate the crude and adjusted associations controlled for the relevant covariates. ResultsAfter exclusion of outliers, for 211 women, crude and adjusted beneficial associations between exposure to higher mean NDVI and HC levels were observed for all the exposure measures. An increase in 1 interquartile range of greenness (100 m buffer) was associated with a statistically significant lower estimated natural log mean HC level (−0.27 95% CI: −0.44; −0.11). The associations were robust to adjustment for covariates. The findings were consistent for different buffers, for the longitudinal approach, when all observations were included in the analysis and slightly stronger associations were observed for women with addresses geocoded at the home or street level. For most of the exposure measures, stronger associations were observed among those of lower sociodemographic status. ConclusionOur findings that more greenness associated with reduced maternal cortisol levels measured in the hair during the first trimester, could have substantial implications for urban planners and public health professional. If our observations will be replicated, it may present a useful avenue for public-health intervention to promote health through the provision of greenness exposure during early pregnancy, specifically to disadvantage populations.

Effects of temperature and food availability on liver fatty acid composition and plasma cortisol concentration in age-0 lake sturgeon: Support for homeoviscous adaptation

Overwintering survival in north temperate fishes involves a series of adaptive responses to multiple environmental stressors. Homeoviscous adaptation includes changes in membrane lipid composition in response to reduced environmental temperature, which may be driven by changes in hormones involved in the endocrine stress response. We examined how reduced temperature and food availability may act in concert to influence hepatic fatty acid composition of phospholipids and triglycerides, in addition to plasma concentration of cortisol in age-0 lake sturgeon (A. fulvescens). At 153 days post hatch (dph), temperature was decreased from 16 °C to 1 °C at a rate of 0.5 °C per day, and at 200 dph, fish were either fed every other day or deprived of food for 45 days to simulate an overwintering event. Liver fatty acid composition of phospholipids and triglycerides were assessed before temperature manipulation (16 °C; 153 dph), when fish had been at 1 °C for 16 days (199 dph), 25 days of overwintering (225 dph) and 45 days of overwintering (245 dph). Plasma cortisol concentration was assessed at 153, 225 and 245 dph. When temperature was decreased, both mono- and polyunsaturated fatty acids significantly increased in phospholipids and triglycerides. Total omega-6 fatty acids significantly increased in phospholipids while total omega-3 fatty acids did not. During the simulated overwintering, there was no obvious difference in fatty acids of phospholipids and triglycerides between diet treatments and no difference in circulating cortisol concentration between baseline and post-stressed fish in the fasted group. Our results provide support for homeoviscous adaptation to cold temperatures in lake sturgeon.

Diurnal variation in serum concentrations of cortisol in captive African (Loxodonta africana) and Asian (Elephas maximus) elephants.

Cortisol is involved in a broad range of physiological processes and enables animals to adapt to new situations and challenges. Diurnal fluctuations in circulating cortisol concentrations in elephants have been demonstrated based on samples from urine and saliva. The aims of this study were to demonstrate diurnal cortisol fluctuations based on blood samples and compare concentrations between seasons, species, and changes in reproductive hormone concentrations. Nine African (Loxodonta africana) and three Asian (Elephas maximus) elephants at two facilities in the United Stateswere included in this study. Blood samples were collected every 2-3 h at one location and every 1-6 h at another. Peak serum concentrations of cortisol averaged 28 ng/ml for both African and Asian elephants, and diurnal cycles included a fivefold decrease from morning peak to evening nadir concentrations. Diurnal cortisol profiles varied uniquely among individual elephants. During the winter, nadir concentrations of cortisol were slightly higher, and the timing of peak concentrations was less predictable. There was no correlation between diurnal serum concentrations of progesterone and cortisol; however, a significant correlation (p = .02) was identified between serum concentrations of testosterone and cortisol when a time lag of ~2-3 h was considered. The physiological significance of the positive correlations between diurnal serum concentrations of cortisol and testosterone in male elephants remains to be determined. If cortisol concentrations are being used to evaluate elephant health or welfare, samples should be obtained at the same time each day to minimize variation due to diurnal fluctuations, and ideally seasonal variations and individuality in diurnal profiles should also be considered.

Evaluation of Prenatal Transportation Stress on the Number of Pituitary Corticotrophs in Mature Brahman Cows

Abstract Prenatal transportation stress (PNS) results in calves that are more temperamental and have greater circulating concentrations of cortisol compared to control calves. The objective of this experiment was to evaluate whether PNS alters the number of pituitary corticotrophs in mature Brahman cows. We hypothesized that the increased circulating cortisol concentrations previously characterized in this bovine model is associated with developmental changes in the anterior pituitary leading to an increased number of corticotrophs. Pregnant Brahman cows (n = 48) were transported in trailers for 2-hour periods at 60±5, 80±5, 100±5, 120±5, and 140±5 days of gestation. Non-transported pregnant cows (n = 48) were designated as the Control group. Control and PNS offspring heifers were managed together under the same environmental conditions. At approximately 5 yr of age, randomly selected non-pregnant cows (Control, n = 8; PNS, n = 6) were humanely harvested and the whole pituitaries were collected. Pituitaries were weighed, fixed in paraformaldehyde, serially dehydrated with graded ethanol, embedded in paraffin blocks, and cut into 5-μm sections. Immunohistochemistry was performed to detect cells expressing adrenocorticotropic hormone (ACTH) as a marker for corticotrophs. Three comparable sections from the midsagittal plane from each animal were processed using an ovine ACTH-specific antibody (Dr. A.F. Parlow, NIDDK). Five fields of view were analyzed per section (15 fields per animal). Anterior pituitary gland weight did not differ (P > 0.10) between groups (Control = 2.11 ± 0.12 g; PNS = 2.10 ± 0.15 g). The mean number of ACTH-positive cells between control (531±56 cells/section) and PNS cows (477±49 cells/section) also did not differ (P > 0.10). In conclusion, the number of pituitary corticotrophs in mature Brahman cows was not affected by prenatal transportation stress and is likely not a mechanism mediating the increased circulating cortisol concentrations seen in this bovine model of fetal programming.

Changes in serum adipokines during natural extended fasts in female northern elephant seals

Adipose tissue is essential to endotherms for thermoregulation and energy storage as well as functioning as an endocrine organ. Adipose derived hormones, or adipokines, regulate metabolism, energy expenditure, reproduction, and immune function in model systems but are less well studied in wildlife. Female northern elephant seals (NES) achieve high adiposity during foraging and then undergo natural fasts up to five weeks long during haul-outs associated with reproduction and molting, resulting in large changes in adipose reserves. We measured circulating levels of four adipokines: leptin, resistin, adiponectin, and kisspeptin-54, in 196 serum samples from female NES at the beginning and end of their breeding and molting fasts. We examined the relationships between these adipokines and life-history stage, adiposity, mass, cortisol, and an immune cytokine involved in the innate immune response interleukin 6 (IL-6). All four adipokines varied with life-history stage. Leptin concentrations were highest at the beginning of the breeding haul-out. Resistin concentrations were higher throughout the breeding haul-out compared to the molt haul-out. Adiponectin concentrations were highest at the beginning of both haul-outs. Kisspeptin-54 concentrations were highest at the end of the breeding haul-out. Leptin, resistin, and adiponectin were associated with measures of body condition, either adiposity, mass, or both. Resistin, adiponectin, and kisspeptin-54 were associated with circulating cortisol concentrations. Resistin was strongly associated with circulating IL-6, a multifunctional cytokine. Adiponectin was associated with glucose concentrations, suggesting a potential role in tissue-specific insulin sensitivity during life-history stages categorized by high adiposity. Increased cortisol concentrations late in lactation were associated with increased kisspeptin-54, suggesting a link to ovulation initiation in NES. This study suggests dramatic changes in circulating adipokines with life-history and body condition that may exert important regulatory roles in NES. The positive relationship between adiponectin and adiposity as well as the lack of a relationship between leptin and kisspeptin-54 differed from model systems. These differences from biomedical model systems suggest the potential for modifications of expression and function of adipose-derived hormones in species that undergo natural changes in adiposity as part of their life-history.

PSV-40 Effects of regrouping and administrations of meloxicam and chromium on plasma cortisol concentrations and behaviors in dairy calves

Abstract This study investigated effects of regrouping and oral meloxicam and chromium administration on growth performance, blood cortisol concentrations, and behaviors in dairy calves. Fifty Holstein calves (average age 196 ± 24.7 days, average body weight 198kg ± 32.7 kg) were equally divided into five groups: no regrouping with lactose monohydrate administration (NL), regrouping with lactose monohydrate administration (GL), regrouping with Cr administration (GC), regrouping with meloxicam administration (GM), and regrouping with both meloxicam and Cr administration (GMC). Blood was collected before regrouping and at 3h, 9h, 24h, 1w, and 2w after regrouping. Behaviors have been monitored from d1 to d7. Regrouping did not affect average daily gain (ADG), and the administrations of both meloxicam and chromium increased (P < 0.02) ADG compared to NL group during 2 weeks. Regrouping increased (P < 0.05) plasma cortisol concentrations in GL group, and both meloxicam and chromium and its combination treatments decreased cortisol concentrations compared to GL group at 24h, but not at other times. Regrouping increased (P < 0.05) fight, duration of eating time, head bunt, drinking time, and standing time behaviors in GL group at d1, d2, d2, d3, and d4 respectively. Regrouping also increased (P < 0.05) displacement at eating place in GL group from d3 to d6, but this effect was not significant (P < 0.05) at d7. In conclusion, regrouping caused elevation of plasma cortisol concentrations and abnormal behaviors. Meloxicam, chromium, and/or its combined administrations improved growth performance and reduced circulating cortisol concentrations in regrouped dairy calves, suggesting a feasible strategy to alleviate regrouping stress.

Endocrine changes related to dog domestication: Comparing urinary cortisol and oxytocin in hand-raised, pack-living dogs and wolves

Dogs are exceptionally well adapted to life close to humans, and alterations in their endocrine system during the domestication process may be an underlying mechanism. In particular, it has been suggested that low circulating cortisol concentrations in conjunction with simultaneously high oxytocin concentrations may have resulted in dogs' increased docility (‘selection for tameness’ hypothesis) and heightened propensity to interact and form relationships with humans (‘hypersociability’ hypothesis) compared to wolves. To investigate this, we analyzed cortisol and oxytocin metabolite concentrations from urine samples of hand-raised, pack-living domestic dogs and their non-domestic relatives, grey wolves. Based on the hypotheses outlined above, we predicted lower cortisol but higher oxytocin concentrations in dogs than wolves. In contrast to our prediction, we found higher cortisol concentrations in dogs than wolves. However, oxytocin concentrations were higher in dogs compared to wolves although the effect was relatively small. Indeed, male dogs had the highest oxytocin concentrations while female dogs' oxytocin concentrations were comparable to wolves'. Feeding status, reproductive phase, and conspecific social interactions also significantly affected cortisol and oxytocin concentrations. Furthermore, we compared two methods of correcting for variable water content of urine samples. We discuss our results in light of physiological and behavioral changes during domestication and highlight the importance of accounting for confounding variables in future studies.

The nonhuman primate hypothalamo-pituitary-adrenal axis is an orchestrator of programming-aging interactions: role of nutrition.

Developmental programming alters life-course multi-organ function and significantly affects life-course health. Recently, interest has developed in how programming may influence the rate of aging. This review describes interactions of nutrition and programming-aging interactions in hypothalamo-pituitary-adrenal (HPA) development and function from fetal development to old age. A full picture of these interactions requires data on levels of HPA activity relating to the hypothalamic, adrenal cortical, circulating blood, and peripheral cortisol metabolism. Data are provided from studies on our baboon, nonhuman primate model both across the normal life course and in offspring of maternal baboons who were moderately undernourished by a global 30% diet reduction during pregnancy and lactation. Sex differences in offspring outcomes in response to similar challenges are described. The data clearly show programming of increased HPA axis activity by moderate maternal undernutrition. Increased postnatal circulating cortisol concentrations are related to accelerated aging of the brain and cardiovascular systems. Future studies should address peripheral cortisol production and the influence of aging advantage in females. These data support the view that the HPA is an orchestrator of interactions of programming-aging mechanisms.

Chronic elevation of plasma cortisol causes differential expression of predominating glucocorticoid in plasma, saliva, fecal, and wool matrices in sheep

There is increasing interest in using nonblood measures of glucocorticoids to assess the physiological response to chronic stress conditions. In sheep, cortisol has been measured in various matrices including saliva, feces, and wool, but comprehensive studies of the relationship between plasma concentrations of cortisol and concentrations in these nonblood matrices are lacking. Therefore, we tested the hypothesis that administration of cortisol to sheep would result in elevated concentrations of cortisol in blood, saliva, feces, and wool. Merino ewes were administered with saline or 2 mg/kg BW/d hydrocortisone acetate (HCA) by intramuscular (i.m.) injection for 28 d. This treatment was imposed to mimic circulating cortisol concentrations experienced during periods of chronic stress. Cortisol and cortisone were directly measured in plasma, saliva, and wool before, during, and after treatment with saline or HCA. A 14-d pre-treatment and a 14-d post-treatment period were used to measure time taken for glucocorticoid concentrations in each of the matrices to return to baseline levels. Cortisol was also measured in feces before, during, and after treatment. Wool growth was also measured. Before treatment, there was no difference in the concentration of cortisol or cortisone in plasma, saliva, feces, or wool in animals treated with saline or HCA. In contrast, treatment with HCA increased (P < 0.05) concentrations of both cortisol and cortisone in plasma, saliva, and wool and of cortisol in feces. In plasma, cortisol concentrations were higher than cortisone (P < 0.05), whereas saliva cortisol and cortisone concentrations did not differ significantly. In wool, the concentration of cortisone was about 19-fold higher than that of cortisol during treatment and post-treatment periods. Treatment with HCA inhibited wool growth. These results demonstrate that an increase in glucocorticoids in the blood of sheep is reflected in increases in saliva (after 7 d of treatment), feces (21 d), and wool (14 d). Therefore, measures of glucocorticoids in these matrices may provide a measure of activation of the adrenal glands over time in sheep, thereby providing a retrospective indicator of chronic stress. With respect to wool, it appears that cortisol is predominantly metabolized to cortisone in the skin or wool follicle and is stored as cortisone. Therefore wool cortisone may also provide an important measure in quantifiying chronic stress in sheep.

Glucocorticoid metabolism in critically ill dogs (Canis lupus familiaris)

Critical illness due to sepsis is a major global health concern associated with a high burden of mortality and cost. Glucocorticoid dysregulation in human sepsis is associated with poorer outcomes. This study examines glucocorticoid metabolism in septic canine patients to delineate elements of cellular dysregulation in common with critically ill humans and explore potential differences. This was a prospective case–control study conducted in the veterinary specialist critical care departments of two University teaching hospitals. Critically ill canine patients with naturally occurring sepsis or septic shock were compared with an in-hospital control population. Serum total, bound, and free cortisol concentrations were increased in septic shock (P < 0.001), and higher bound cortisol was associated with nonsurvival (P = 0.026). Urinary Gas Chromatography-Tandem Mass Spectrometry was performed to assess urinary glucocorticoid metabolites and estimate intracellular glucocorticoid metabolism. Decreased renal 11β-hydroxysteroid dehydrogenase 2 (11βHSD2) activity inferred from increased urinary cortisol-to-cortisone ratio was observed in critically ill dogs (P < 0.001). Decreased 11βHSD2 activity (P = 0.019) and increased A-ring reduction of cortisone (P = 0.001) were associated with nonsurvival within the critically ill dogs. Intriguingly, two dogs were identified with low circulating total cortisol (<2 mg/dL) associated with increased A-ring reduction of cortisol, not previously described. Investigation of spontaneous canine sepsis and septic shock reveals dysregulation of cortisol to cortisone conversion similar to that observed in human patients, but with differences in A-ring reduction compared with those reported in humans. In addition, two dogs with high levels of cortisol inactivation associated with low circulating cortisol concentrations were identified.

Plasma Β-Endorphin and Cortisol Profiles around Periparturient Period at Stressful Conditions in Egyptian Buffalo

&lt;p&gt;The study determined the level of plasma β-endorphin and cortisol concentrations in peripheral blood circulation of buffalo cows suffering from reproductive disorders (dystocia and retained placenta) and weakness body condition score during periparturient period. Twenty multi-parous Egyptian buffalo cows at late pregnancy period were used for two months before parturition. β-endorphin concentrations were higher in buffalo suffering from reproductive disorders groups. Whereas, β-endorphin concentrations were 134.9±4.8 for retained placenta, 121.3±4.9 for dystocia, 114.2±8.4 for weakness and 113.5±6.5 pg/ml for control. In the closer period around parturition both of plasma β-endorphin and cortisol followed the same trend toward a gradually increased values during -2,-1days and zero time in all groups. A concomitant trend was noticed in β-endorphin and cortisol concentrations in postpartum period with reduce values were observed in all groups after parturition continued for month or more. Buffalo suffering from reproductive disorders were showed a high relative values in β-endorphin and cortisol concentrations. A significant differences (P&amp;lt;0.01) were observed between the experimental groups. Generally, buffaloes suffering reproductive disorders had a clear impact on blood plasma β-endorphin concentration around parturition process.&lt;/p&gt;&lt;p&gt;The aim of this study was to determine the relationship between various reproductive disorders as a stress factors with plasma β–endorphin and cortisol in buffalo cows around parturition and changes in these parameters could be used as an objective measure of the stress associated labour. Stress has been hypothesized to be a cause of impaired reproductive efficiency. Stress may cause an overproduction of beta-endorphins and free radicals&lt;/p&gt;

Comparative assessment of cortisol in plasma, skin mucus and scales as a measure of the hypothalamic-pituitary-interrenal axis activity in fish

Cortisol, the end product of the hypothalamus-pituitary-interrenal (HPI) axis, has been traditionally measured in blood as indicator of stress in fish, however, the degree of invasiveness inherent to blood collection is not always possible or desirable. Instead, cortisol measurement in skin mucus is far less invasive, but as blood, this method potentially provides only a brief window of information of the HPI axis activity. The newly described method of cortisol measurement from scales may serve as a long-term, integrated measure of the HPI axis activity in fish. While skin mucus and scales cortisol measurement present practical and conceptual advantages, there are still several unclear issues related to their biological relevance that need deeper study. Accordingly, we aimed to evaluate whether skin mucus and scales cortisol levels can be reliably used as stress indicators by subjecting fish to prolonged, continuous stressful conditions. The present study demonstrates that the measurement of cortisol in skin mucus reflect circulating cortisol concentrations when fish are responding to stress with an intense activation of the HPI axis. Results also revealed that cortisol content in scales strongly correlates to circulating cortisol levels in chronically stressed fish. Besides, we provide further support that scales cortisol assessment offer a retrospective measure of the past stress experience in fish. While this study provides a good basis for future research applying the methods presented, our results open the question of whether these matrices have additional sources of cortisol other than blood, and the route of incorporation or diffusion. Further knowledge about the general robustness and stability of scales cortisol in fish subjected to prolonged stress would largely help strengthen the interpretation of hormone fluctuations in this matrix.

Effects of castration and a lidocaine-plus-flunixin treatment on growth and indicators of pain, inflammation, and liver function in Korean cattle bull calves

The aim of this study was to determine the effects of castration and a lidocaine-plus-flunixin (LF) treatment on growth and indicators of pain, inflammation, and liver function in Korean cattle bull calves. Forty Korean cattle bull calves (body weight 197.0 ± 2.94 kg and age 6.3 ± 0.09 months) were each assigned to one of four treatments (n = 10 heads/group): no castration with no LF injection (NC-NLF); no castration with LF injection (NC-LF); castration with no LF injection (C-NLF); and castration with LF injection (C-LF). LF treatment included a local anesthetic lidocaine hydrochloride injection (12 mL of 2% in the scrotum) and intravenous injection of a non-steroidal anti-inflammatory drug, flunixin meglumine (2 mg/kg body weight of 50 mg/mL solution), immediately prior to castration. For the NLF groups, a 0.9% NaCl placebo solution was used. Castration was performed surgically using a Newberry knife and a Henderson castrating tool. Blood was collected immediately before castration and at h 0.5, h 6, d 1, d 3, d 7, and d 14 after castration. Feed intake was recorded daily, and body weight was measured on the day prior to the experiment and at d 14 after castration. Castration tended (P = 0.07) to decrease average daily weight gain, but LF treatment did not affect weight gain. Castration increased both circulating cortisol concentrations (P < 0.001) at h 0.5 after castration and substance P (SP) concentrations (P = 0.001) at h 6 after castration. However, the LF treatment did not significantly reduce cortisol and SP concentrations in castrated animals. Castration increased (P < 0.001) circulating haptoglobin (Hp) concentrations on d 1 and d 3 after castration, and LF treatment tended (P = 0.09) to decrease Hp concentrations on d 1 and decreased (P = 0.02) Hp concentrations on d 3. Castration did not affect glutamic oxaloacetic transaminase (GOT) and glutamic pyruvate transaminase (GPT) concentrations. LF treatment increased GOT concentrations at h 6 (P < 0.001), d 1 (P < 0.001), and d 3 (P = 0.003). LF treatment also increased GPT concentrations on d 1 (P = 0.006) and d 3 (P = 0.003). In conclusion, castration of bull calves resulted in time-sequential increases in circulating concentrations of cortisol at h 0.5, SP at h 6, and Hp on d 1. LF treatment did not significantly reduce elevated cortisol and SP, but tended to decrease elevated Hp concentrations in castrated animals. Our study demonstrates that LF treatment is not sufficient for the reduction of the indicators of pain and inflammation in castrated calves, suggesting that additional alleviation methods are required.

Cortisol during adolescence organises personality traits and behavioural syndromes

Despite the growing evidence for the importance of developmental experiences shaping consistent individual differences in behaviour and physiology, the role of endocrine factors underlying the development and maintenance of such differences across multiple traits, remains poorly understood. Here, we investigated how an experimental manipulation of circulating glucocorticoids during early adolescence affects behavioural and physiological variation and covariation later in life in the precocial cavy (Cavia aperea). Plasma cortisol concentrations were experimentally elevated by administering cortisol via food for 3 weeks. Struggle docility, escape latency, boldness, exploration and social behaviour were then tested three times after individuals attained sexual maturity. In addition, blood samples were taken repeatedly to monitor circulating cortisol concentrations. Exogenous cortisol affected mean trait expression of plasma cortisol levels, struggle docility and escape latency. Repeatability of cortisol and escape latency was increased and repeatability of struggle docility tended to be higher (approaching significance) in treated individuals. Increased repeatability was mainly caused by an increase of among-individual variance. Correlations among docility, escape latency and cortisol were stronger in treated animals compared to control animals. These results suggest that exposure to elevated levels of cortisol during adolescence can alter animal personality traits as well as behavioural syndromes. Social and risk-taking traits showed no correlation with cortisol levels and were unaffected by the experimental manipulation, indicating behavioural modularity. Taken together, our data highlight that cortisol can have organising effects during adolescence on the development of personality traits and behavioural syndromes, adding to the increasing evidence that not only early life but also adolescence is an important sensitive period for behavioural development.

Evidence for cortisol-cortisone metabolism by marine mammal blubber.

Blubber, a specialized hyperdermic adipose tissue found in marine mammals, has been identified as a useful tissue for the assessment of steroid hormone homeostasis in cetaceans. However, blubber cortisol measurements are not quantitatively predictive of circulating cortisol concentrations in bottlenose dolphins. In other mammals, adipose tissue metabolizes steroid hormones. Thus, it is proposed that the disagreement between blubber and blood cortisol in bottlenose dolphins could be due in part to metabolism of corticosteroids in blubber. The purpose of this study is to characterize the ability of blubber to interconvert cortisol and cortisone using an in vitro design. Results demonstrate that bottlenose dolphin blubber microsomes interconvert cortisol and cortisone, an effect that is abated by denaturing the microsomes, indicating this is an enzymatic process. These findings lead to the conclusion that blubber is likely a site of active steroid metabolism, which should be considered in future studies utilizing blubber as a matrix for endocrine assessment.