Changes In Corticosterone Levels Research Articles

Plasma Osteopontin Modulates Chronic Restraint Stress-Induced Thymus Atrophy by Regulating Stress Hormones: Inhibition by an Anti-Osteopontin Monoclonal Antibody

Osteopontin (OPN) is a cytokine implicated in mediating responses to certain stressors, including mechanical, oxidative, and cellular stress. However, the involvement of OPN in responding to other physical and psychological stress is largely unexplored. Our previous research revealed that OPN is critical for hind limb-unloading induced lymphoid organ atrophy through modulation of corticosteroid production. In this study, we demonstrate that OPN(-/-) mice are resistant to chronic restraint stress (CRS)-induced lymphoid (largely thymus) organ atrophy; additionally, the stress-induced up-regulation of corticosterone production is significantly reduced in OPN(-/-) mice. Underlying this observation is the fact that normal adrenocorticotropic hormone levels are substantially reduced in the OPN(-/-) mice. Our data demonstrate both that injection of OPN into OPN-deficient mice enhances the CRS-induced lymphoid organ atrophy and that injection of a specific anti-OPN mAb (2C5) into wild-type mice ameliorates the CRS-induced organ atrophy; changes in corticosterone levels were also partially reversed. These studies reveal that circulating OPN plays a significant role in the regulation of the hypothalamus-pituitary-adrenal axis hormones and that it augments CRS-induced organ atrophy.

Effects of stress, mimicked by administration of corticosterone in drinking water, on the expression of chicken cytokine and chemokine genes in lymphocytes

In this study, we identify molecular mediators that participate in the regulation of the immune response during corticosterone-induced stress in chickens. At 7 weeks of age, 120 chickens were exposed for 1 week to corticosterone treatment. Cytokine and chemokine mRNA expression levels were evaluated in peripheral blood and splenic lymphocytes. Expression levels of interleukin (IL)-1β, IL-6, IL-18 and transforming growth factor (TGF)-β4 mRNA were significantly up-regulated in lymphocytes 3 h after first treatment with corticosterone. TGF-β4 and IL-18 remained elevated 1 week post-initial treatment. Compared with controls, corticosterone-treated birds showed greater expression levels of chemokine (CC) mRNA, particularly for CCLi2, CCL5 (RANTES), CCL16 and CXCLi1, in peripheral and splenic lymphocytes 3 h post-initial exposure. CCLi2 mRNA was highly expressed in splenocytes at all time-points. Administration of corticosterone significantly increased circulating corticosterone concentrations and decreased total lymphocyte counts at 3, 24 h and 1 week post-initiation of corticosterone treatment. There was a positive correlation between plasma corticosterone concentrations and CCL5 and CCL16 mRNA at 3 h post-initial administration. At 1 week post-initial treatment, corticosterone concentrations correlated positively with CCL5 and negatively with IL-18 mRNA level. Conditions associated with significant changes in corticosterone levels might therefore affect the immune response by increasing pro-inflammatory responses, leading to potential modulation of the Th1/Th2 balance.

Neurohormonal changes during formation of latent inhibition in rats predisposed to catalepsy

The response of two monoaminergic systems to induction of latent inhibition has been studied in two rat strains. The noradrenergic system of the Wistar rat brain responded uniformly and systemically in the hippocampus, hypothalamus, amygdala, and frontal cortex. It has been shown that footshock induced a decrease in the norepinephrine level and the return of the mediator level to the control level in the “adaptation + footshock” groups for the four brain regions studied. Significant differences in norepinephrine levels were found in the “footshock” group in the hippocampus and hypothalamus of Wistar rats but not GC rats. The lowest serotonin level in the hippocampus was found in the “adaptation + footshock” group of the cataleptic strain. Opposite changes in corticosterone levels in the blood plasma of GC and Wistar rats were significant according to the F test (F[2, 70] = 3.908, p < 0.05). Differences in the testosterone levels between the two strains during induction of the latent inhibition were absent.

High doses of dietary zinc induce cytokines, chemokines, and apoptosis in reproductive tissues during regression

In chickens, high levels of dietary zinc cause molting, and the reproductive system undergoes complete remodeling concomitant to feather replacement. In the present study, the expression profiles of cytokines and chemokines were investigated in the ovary and oviduct of control hens and of hens induced to molt by zinc feeding. The zinc-induced feed-intake suppression, the changes in corticosterone levels, the immune cell populations in the reproductive tract, and the apoptosis of reproductive tissues were analyzed. The expression of mRNAs for interleukin-6 (IL-6), interferon-gamma (IFN-gamma), the avian ortholog of mammalian IL-8 (chCXCLi2), and a chicken MIP-1beta-like chemokine (chCCLi2) in the ovary and of mRNAs for IL-1beta, IL-6, IFN-gamma, transforming growth factor-beta2, chCXCLi2, and chCCLi2 in the oviduct were upregulated significantly during zinc-induced molting. A simultaneous feed-intake reduction was observed with higher expression of cytokines and chemokines. The results of the present investigation also suggested that the upregulation of corticosterone was closely associated with the increased expression of cytokines and chemokines. An increase in apoptosis within reproductive tissue during tissue regression was also noted. We had previously observed the upregulation of these cytokines expression in an earlier study (molting by feed withdrawal). However, the pattern and the level of expression were different among these two methods. These findings indicate that cytokines might be a common mediator of tissue regression during molting induced by diverse methods, although the pattern of induction is different. Thus, a high dose of dietary zinc seems to induce reproductive regression via the upregulation of cytokines and chemokines, the suppression of feed intake, and the increase in serum corticosterone, resulting finally in the apoptosis of reproductive tissues.

Monitoring glucocorticoid response to rehabilitation and research procedures in California and Steller sea lions

We used serum and fecal corticosteroid analysis to study the physiological response to a range of invasive and non-invasive procedures in sea lions. Four experimental groups of California sea lions (Zalophus californianus; Group A: restraint only [n=9], Group B: gas anesthesia without surgery [n=10], Group C: minimally invasive surgery [n=10], and Group D: invasive surgery [n=5]) were monitored for adrenal response. Feces were collected opportunistically from 72 hr before 72 hr post procedure for corticosterone analysis. All experimental groups showed substantial individual variation and no significant change in corticosterone levels after the procedures. Additional fecal and serum corticoid samples were collected from six free-ranging Steller sea lions (Eumetopias jubatus) in temporary captivity undergoing abdominal implantation of long-term telemetry devices. Only one sea lion exhibited a significant fecal corticosterone increase in response to the surgery. Capture and restraint appear to elicit a greater glucocorticoid response than invasive or non-invasive procedures.

Protective Effect of Triphala on Cold Stress-induced Behavioral and Biochemical Abnormalities in Rats

Stress is one of the basic factors in the etiology of number of diseases. Cold-stress occurs when the surrounding temperature drops below 18 degrees C, the body may not be able to warm itself, and hence serious cold-related illnesses, permanent tissue damage and death may results. The present study was aimed to investigate the effect of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) against the cold stress-induced alterations in the behavioral and biochemical abnormalities in four different groups (saline control, Triphala, cold-stress and Triphala with cold-stress) of Wistar strain albino rats. In this study cold-stress (8 degrees C for 16 h/d/15 days) was applied and the oxidative stress was assessed by measuring the extent of lipid peroxidation (LPO) and the changes in corticosterone levels. Upon exposure to the cold-stress, a significant (P<0.05) increase in immobilization with decrease in rearing, grooming, and ambulation behavior was seen in open field. Following cold-exposure, significant increase in the LPO and corticosterone levels was observed. Oral administration of Triphala (1 g/kg/animal body weight) for 48 days significantly prevented these cold stress-induced behavioral and biochemical abnormalities in albino rats. The results of this study suggest that Triphala supplementation can be regarded as a protective drug against stress.

Triiodothyronine suppresses humoral immunity but not T-cell-mediated immune response in incubating female eiders ( Somateria mollissima)

Immunity is believed to share limited resources with other physiological functions and this may partly account for the fitness costs of reproduction. Previous studies have shown that the acquired immunity of female common eiders ( Somateria mollissima) is suppressed during the incubation fast. To save energy, triiodothyronine (T 3) is adaptively decreased during fasting in most bird species, despite T 3 levels are maintained throughout incubation in female eiders. However, the relationship between thyroid hormones and the immune system is not fully understood. The current study aimed to determine the endocrine mechanisms that underlie immunosuppression in incubating female eiders. To this end we assessed the effects of exogenous T 3 on both components of the acquired immune system in 42 free-ranging incubating birds. Half of the females were implanted with T 3 pellets, while the other half sham implanted served as control. We measured variations in the immunoglobulin index, the T-cell-mediated immune response, body mass, and plasma parameters in both groups before and after manipulation. T 3 levels in implanted females were four times higher and mass loss was 40% greater than in control females. Implanted females also showed an 18% decrease in the immunoglobulin index, while the T-cell-mediated immune response was not significantly affected by the treatment. Finally, the treatment did not induce any significant changes in corticosterone levels. Our study shows that exogenous T 3 decreased only one component of the acquired immune system. We suggest that the immunosuppressive effect of T 3 could be mediated by its effects on body fat reserves. Further experiments are required to determine: (1) the relationship between adiposity and immune function, (2) the adaptive significance of immunosuppression during incubation in eiders.

The effects of individual housing on mice and rats: a review

AbstractIsolating an animal refers to the situation where the animal is physically fully demarcated from conspecifics without physical, visual, olfactory and auditory contact. Animals housed in separate cages in the same room are, although deprived of physical and visual contact, still in olfactory and auditory contact, and thus not totally isolated. During the fifties and sixties several studies claimed to show physiological and behavioural differences between individually and group housed rats and mice. The so-called ‘Isolation Syndrome’ characterised by changes in corticosterone levels, metabolism, growth, and behaviour was introduced, rather as a model for psychoneurosis than through any concern for animal welfare. Today, it is often stated as common knowledge in laboratory animal science textbooks that individual housing as well as isolation of rats and mice has an effect on physiology and behaviour. It is, however, unclear whether this effect actually impairs animal welfare.The aim of this paper is to analyse studies on individual housing of mice and rats to evaluate whether there is documented proof that individual housing affects welfare, and, alternatively whether it is possible to house these animals individually without negative impact on welfare, eg by providing special housing improvements.A range of studies have shown that individual housing or isolation has effects on corticosterone, the open field behaviour, barbiturate sleeping time and the metabolism of different pharmaceuticals in the animals. However, this review of 37 studies in rats and 17 studies in mice showed divergence in test results difficult to explain, as many studies lacked basal information about the study, eg information on genetic strains and housing conditions, such as bedding, enrichment and cage sizes. Furthermore, test and control groups most frequently differed in cage sizes and stocking densities, and behavioural tests differed in ways which may very well explain the differences in results. Overall, there seemed to be an effect of individual housing, although it may be small, and it seems reasonable to assume that, through making small changes in the procedures and housing environments, the effects can be minimised or even eliminated. More well-controlled and standardised studies are needed to give more specific answers to the questions this issue poses.

Effects of Antidepressants on the Brain/Plasma Distribution of Corticosterone

It is well established that hypothalamic-pituitary-adrenal (HPA) axis dysregulation, characterized by elevated circulating cortisol concentrations and impaired negative feedback inhibition, is associated with affective disorders. As normalization of the HPA axis function and mood-stabilizing effects occur simultaneously during antidepressant treatment, it is likely that these effects are either directly or indirectly dependent. Although data concerning the outward transport of glucocorticoids from the brain by P-glycoprotein (Pgp) are inconsistent, it has been hypothesized that antidepressants exert their clinical activity in parts by inhibiting Pgp, subsequently leading to enhanced brain glucocorticoid levels and the normalization of the HPA axis function. Here, we report on the effects of different antidepressants (amitriptyline, fluoxetine, mirtazapine, St John's wort extract) on the brain/plasma distribution of corticosterone in mice after acute and subchronic treatment. The four antidepressants exerted different effects on the corticosterone concentration in brain and plasma. Changes in corticosterone levels were highly correlated, suggesting passive diffusion between both tissues. St John's wort extract and fluoxetine elevated brain and plasma corticosterone concentrations after subchronic treatment. Mirtazapine and amitriptyline had no effect on corticosterone concentration after subchronic treatment, possibly because both are also potent antagonists at the 5-HT2 receptor, which mediates HPA axis stimulation by serotonergic stimuli. In addition, St John's wort is the only antidepressant tested which slightly elevated Pgp protein level in the brain.

Protein synthesis and the mechanisms of lasting change in anxiety induced by severe stress

Brief, unprotected exposure of rats to cats (predator stress) may be lastingly anxiogenic in a variety of tests of rodent anxiety. Recent findings suggest that predator stress induced plasticity in neural circuitry implicated in fear learning underlies some of these anxiogenic effects. In addition, recent work implicates a consolidation-like process in the impact of predator stress on anxiety in that effects of predator stress may be interrupted by immediate post stressor pharmacological interventions. The present study tested whether “consolidation” of the anxiogenic effects of predator stress were dependent on protein synthesis. In addition, the study examined whether a protein synthesis dependent reconsolidation-like process was at work when rats were exposed to a cat twice. Anisomycin (210 mg/kg) or vehicle (Tween 80 in saline) was injected subcutaneously 1 min after a single cat exposure (consolidation test paradigm) or a 1 min after a second cat exposure (reconsolidation test paradigm) and behavior tested 7–8 days after predator stress. In the consolidation test paradigm, anisomycin blocked the anxiogenic effects of predator stress in the elevated plus maze (EPM) measured with open arm exploration. Moreover, anisomycin blocked the potentiation of startle by predator stress when rats were startled in the light, but not when startled in the dark. In contrast, the delay of habituation of startle produced by predator stress was unaffected by anisomycin. Suppression of risk assessment in the EPM by predator stress was not affected by anisomycin either. In startle testing, vehicle injection 1 min after predator stress led to a lasting suppression, rather than enhancement of startle response. Vehicle plus predator stress enhanced and prolonged corticosterone level changes sampled over 30–180 min after treatment when compared to handled or predator stressed only rats. In addition, predator stress plus vehicle suppression of startle was blocked by a benzodiazepine anxiolytic (chloradiazepoxide) or the glucorticoid receptor (GR) blocker RU486. Both drugs returned startle to the predator stressed only heightened levels. It is argued that an added anxiogenic effect of vehicle injection plus predator stress leads to a suppression, rather than enhancement of startle. Startle suppression appears to be mediated, in part, by activation of GR by corticosterone which engages a protein synthesis dependent process, since anisomycin blocked the startle suppressive effects of vehicle. Startle suppression also appeared to be independent of the startle enhancing effect of predator stress and in competition with it. Since predator stress may model aspects of hyperarousal associated with post traumatic stress disorder (PTSD), implications of these findings for understanding of mechanisms of initiation of the disorder and for treatment are discussed.

Differential behavioral and neuroendocrine effects of repeated nicotine in adolescent and adult rats

Despite the high prevalence of tobacco abuse among adolescents, the neurobiology of nicotine addiction has been studied mainly in adult animals. Repeated administration of this drug to adult rats induces behavioral sensitization. Nicotine activates the HPA axis in adult rats as measured by drug-induced increases in ACTH and corticosterone. Both behavioral sensitization and corticosterone are implicated in drug addiction. We examined the expression of behavioral sensitization induced by nicotine as well as the changes in corticosterone levels after repeated injections of nicotine in adolescent and adult animals. Adolescent and adult rats received subcutaneous (s.c.) injections of saline or 0.4 mg/kg of nicotine once daily for 7 days. Three days after the last injection animals were challenged with saline or nicotine (0.4 mg/kg; s.c.). Nicotine-induced locomotion was recorded in an activity cage. Trunk blood samples were collected in a subset of adolescent and adult rats and plasma corticosterone levels were determined by radioimmunoassay. Adult, but not adolescent, rats expressed behavioral sensitization. Pretreatment with nicotine abolished corticosterone-activating effect of this drug only in adult animals, indicating the development of tolerance at this age. Our results provide evidence that adolescent rats exposed to repeated nicotine display behavioral and neuroendocrine adaptations distinct from that observed in adult animals.

Age-specific threats induce CRF expression in the paraventricular nucleus of the hypothalamus and hippocampus of young rats

Young animals respond to threatening stimuli in an age-specific way. Their endocrine and behavioral responses reflect the potential threat of the situation at a given age. The aim of the present study was to determine whether corticotropin-releasing factor (CRF) is involved in the endocrine and behavioral responses to threat and their developmental changes in young rats. Preweaning 14-day-old and postweaning 26-day-old rats were exposed to two age-specific threats, cat odor and an adult male rat. The acute behavioral response was determined during exposure. After exposure, the time courses of the corticosterone response and of CRF expression in the paraventricular nucleus of the hypothalamus (PVN) and in extrahypothalamic areas were assessed. Preweaning rats became immobile when exposed to cat odor or the male rat, whereas postweaning rats became immobile to cat odor only. Male exposure increased serum corticosterone levels in 14-day-old rats, but cat odor failed to increase levels at either age. Exposure induced elevation of CRF mRNA levels in the PVN that paralleled changes in corticosterone levels. CRF may thus play a role in endocrine regulation and its developmental changes during early life. Neither cat odor nor the adult male altered CRF mRNA levels in the bed nucleus of the stria terminalis (BNST) or the amygdala, but both stimuli increased levels in the hippocampus. Hippocampal CRF mRNA expression levels did not parallel cat odor or male-induced immobility, indicating that CRF is not involved in this response in young rats but may be involved in aspects of learning and memory.

Reactivity of the Hypophyseal-Adrenocortical System to Stress in Rats with Active and Passive Behavioral Strategies

Rats with active (KHA) and passive (KLA) behavioral strategies showed no strain-related differences in basal corticosterone levels or in changes in corticosterone levels after exposure to mildly stressful stimuli. Only severe immobilization stress produced significant interstrain differences in the reactivity of the hypophyseal-adrenocortical system, as evidenced by the greater increase in blood corticosterone in KHA rats 30 min after stressing. The hormonal stress response in KHA rats was prolonged, as the elevated blood corticosterone level in these animals persisted longer than in KLA rats. The data provide evidence not only that the hypophyseal-adrenocortical systems have different sensitivities to severe stresses in these strains, but also that active and passive animals have different rates of inactivation of the stress reaction.

GABA receptor modulation of 5-HT neuronal firing: characterization and effect of moderate in vivo variations in glucocorticoid levels

Evidence from electrophysiological studies suggests that 5-HT neuronal firing in the dorsal raphe nucleus (DRN) may be regulated by both GABA A and GABA B receptors. Here, we addressed the question of whether the activity of individual 5-HT neurons is regulated by both GABA A and GABA B receptors. In addition, we examined the concentration-response relationships of GABA A and GABA B receptor activation and determined if GABA receptor regulation of 5-HT neuronal firing is altered by moderate alterations in circulating corticosterone. The activity of 5-HT neurons in the DRN of the rat was examined using in vitro extracellular electrophysiology. The firing of all individual neurons tested was inhibited by both the GABA A receptor agonist 4,5,6,7-tetrahydroisoxazolo-[5,4-c]-pyridin-3-ol hydrochloride (THIP) (25 μM) and the GABA B receptor agonist baclofen (1 μM). Responses to THIP (5, 10, 25 μM) and baclofen (1, 3, 10 μM) were concentration dependent and attenuated by the GABA A and GABA B receptor antagonists, bicuculline (50 μM) and phaclofen (200 μM), respectively. To examine the effects of corticosterone on the sensitivity of 5-HT neurons to GABA receptor activation, experiments were conducted on adrenalectomized animals with corticosterone maintained for two weeks at either a low or moderate level within the normal diurnal range. These changes in corticosterone levels had no significant effects on the 5-HT neuronal response to either GABA A or GABA B recepter activation. The data indicate that the control of 5-HT neuronal activity by GABA is mediated by both GABA A and GABA B receptors and that this control is insensitive to moderate changes in circulating glucocorticoid levels.

Endogenous activation of group-II metabotropic glutamate receptors inhibits the hypothalamic–pituitary–adrenocortical axis

Systemic injection of the mGlu2/3 receptor antagonist, LY341495 (1 mg/kg, i.p.), increased plasma corticosterone in mice to an extent similar to that induced by the despair test. Treatment with the mGlu2/3 receptor agonist, LY379268 (1 mg/kg, i.p.), or the non-competitive mGlu5 receptor antagonist, MPEP (5 mg/kg, i.p.), failed to induce significant changes in corticosterone levels. Searching for a site of action of LY341495, we examined the expression of mGlu receptor subtypes in the various anatomical regions of the mouse hypothalamic–pituitary–adrenal (HPA) axis. Only mGlu5 and -7 receptor mRNAs were detected in the adrenal gland by RT-PCR, whereas mGlu -1, -3, -4, -5, -7 and -8 receptor mRNAs were detected in the anterior pituitary. All transcripts (with the exception of mGlu5 and mGlu6 receptor mRNAs) were detected in the hypothalamus. However, Western blot analysis showed the presence of mGlu2/3 receptor proteins only in the hypothalamus and not in the anterior pituitary. This was consistent with functional data showing that LY341495 (0.1 and 1 μM) failed to affect ACTH secretion from isolated mouse anterior pituitaries. Moving from these observations, we examined whether LY341495 could activate the HPA axis by inhibiting mGlu2/3 receptors at hypothalamic level. We measured the release of corticotropin releasing hormone (CRH) in isolated mouse hypothalami incubated in the presence of subtype-selective mGlu receptor agonists or antagonists. Among all the drugs we have tested, only LY341495 was able to increase CRH secretion. With high concentrations of LY341495 (1 μM) this increase was similar to that induced by 50 mM K +. The action of LY341495 was prevented by the combined application of the mGlu2/3 receptor agonist, LY379268. We conclude that group-II mGlu receptors tonically regulate the HPA axis by controlling CRH secretion at hypothalamic level.

A delayed increase in hippocampal proliferation following global asphyxia in the neonatal rat

Adult neurogenesis has been shown to be upregulated following a wide variety of brain injury paradigms. During the first weeks of postnatal life there is around 50 fold more neurogenesis occurring than in the adult CNS, yet little is known regarding the effect of neonatal brain injury on this developmental proliferation. We have investigated the effect of a global perinatal birth asphyxia on postnatal proliferation at 2, 5, 8, 11, 15, 21 and 28 days after birth (injury) using a 3H-thymidine tracer study. We found a specific upregulation of proliferation at 5 days after the injury within the injured hippocampus only, with an associated increase in hippocampal mass and without any changes in GFAP content at any timepoint. Perinatal asphyxia did not alter proliferation within the cerebellum, sub ventricular zone, olfactory bulb, cervical or thoracic spinal cord. Similarly, no changes in corticosterone levels were induced by the injury. Since there were no changes in GFAP content we hypothesize that this increased proliferation is likely neurogenetic, similar to what is seen in the adult brain following injury. Further we show that the dramatic increase in corticosterone at the end of the stress hyporesponsive period is not responsible for the equally dramatic decrease in postnatal proliferation within the CNS.

Body weight gain and diurnal differences of corticosterone changes in response to acute and chronic stress in rats

Plasmatic levels of corticosterone display a circadian rhythm, with the higher values occurring during the dark phase in nocturnally feeding animals. Stressful situations induce a rise of corticosterone levels and this endocrine response to stress also presents circadian variations. The higher increase of corticosterone in response to stress occurs when the hormone is in its lower circadian level, and the minimum responses occurring at the peak. Since it has been shown that plasma hormones respond differently to different stressors, in the present study, we compared the acute and chronic effects of four different stressors: electric foot shocks (3 mA, 1/s, 5 min), immobilization during two hours or six hours, and immersion in cold water (15°C) for 15 min. Stressors were applied, both acutely and chronically (during 4, 12 and 20 days) at the onset of the light phase as well as at the onset of the dark phase of the light/dark cycle. Body weight was assessed every day, and at the end of the manipulations plasmatic corticosterone levels were determined from the trunk blood. Adrenal and testicular weights were also assessed. Acute exposure to stressors increased plasmatic corticosterone levels significantly when the stressors were applied at the beginning of the light phase of the cycle. In the dark phase, only two hours of immobilization and immersion in cold water caused an increase in plasmatic corticosterone. With repeated exposure, electric foot shocks failed to induce significant changes in corticosterone levels in any phase of the light–dark cycle. Immobilization stress induced a significant rise in corticosterone levels only when the stressor was applied during the light phase. Immersion in cold water elicited a clear increase in plasmatic corticosterone levels in all the periods tested, regardless of the time of the cycle in which the stressor was applied. We did not observe a loss in body weight, but rather a smaller weight gain in stressed rats. Body weight gain was minimum in rats exposed to immersion and 6 hours of immobilization. Adrenal hypertrophy was observed in rats exposed to these same stressors. We conclude that: 1) the activation of the hypothalamus-pituitary-adrenal axis by stress depends mainly on the characteristics of the stressor; 2) the response of this axis to stress also depends on the time of day in which the stressor is applied.

Sight of a Predator Can Stimulate a Corticosterone Response in the Great Tit (Parus major)

The corticosterone response to the sight of a natural predator was investigated in free-living and captive great tits (Parus major). Free-living great tits responded to the sight of a stuffed, slowly moving Tengmalm's owl, a major predator of great tits, with warning calls and a change in behaviour around a feeder. Great tits returned to the feeder within a few minutes and began to approach the owl, and there was no increase in plasma corticosterone levels in birds sampled 30–50 min after they first saw the owl. Captive great tits in an aviary were exposed for 30 min to a stuffed Tengmalm's owl, to a stuffed brambling, and to a cardboard box. All three stimulus objects were slowly rotated during the exposure period. Great tits exposed to the owl changed their behaviour immediately, and spent most of the time when the owl was visible flying around the aviary and hanging from the roof, with very few visits to a feeder. Great tits exposed to the brambling and to the moving box also changed their behaviour and made fewer visits to the feeder. The great tits responded to the sight of the owl with a marked increase in plasma corticosterone levels, whereas there was no change in corticosterone levels (mean levels < 11 ng/ml) in birds exposed to the brambling or to the moving box. Mean corticosterone levels were high (37.1 ± 4.9 ng/ml) 0.5 h after exposure to the owl, remained high (38.9 ± 6.0 ng/ml) 1 h after exposure, and had returned to basal (5.3 ± 1.3 ng/ml) 3 h after exposure to the owl. This is the first demonstration for any bird of a complete corticosterone response to a predator. The sight of a predator initiated a corticosterone response in great tits that could not move more than 3 m away, whereas free-living great tits that could choose how far to fly away from the predator either did not initiate a corticosterone response, or had a small corticosterone response in which corticosterone levels were not significantly different from basal 30–50 min later. The results indicate that the initiation of a corticosterone response in birds depends on whether or not a bird perceives that a stimulus is a threat. Furthermore, they illustrate the importance of not making generalised conclusions based on laboratory experiments.

USING A COMMERCIALLY AVAILABLE RADIOIMMUNOASSAY TO QUANTIFY CORTICOSTERONE IN AVIAN PLASMA

Abstract Using a commercially available corticosterone I125 double-antibody radioimmunoassay, we developed and validated an assay procedure for determining corticosterone levels in small-volume (≤30 μL) avian plasma samples. We evaluated this procedure's utility by measuring plasma corticosterone levels in Indigo Buntings (Passerina cyanea), American Goldfinches (Carduelis tristis), Red-eyed Vireos (Vireo olivaceus), and Mourning Doves (Zenaida macroura). Standard biochemical validations (e.g., parallelism, recovery of exogenous corticosterone) demonstrated that the assay accurately and precisely measured corticosterone in avian plasma. We used a stress capture protocol to physiologically validate the assay's ability to determine biologically important changes in corticosterone levels. Males and females from four bird species exhibited a significant increase in plasma corticosterone in response to capture, handling, and restraint. Baseline and stress-induced corticosterone levels in our study were similar...

Adrenalitis in the Non-obese Diabetic Mouse

The non-obese diabetic (NOD) mouse is a model of spontaneous type-1 diabetes used in the field of diabetes research. This study looked at the adrenal glands of NOD and control mice both indirectly in vivo for hormone secretion, and directly in vitro for histological examination. Adrenal glands were taken from NOD mice, of both sexes, at different ages and corticosterone and adrenocorticotropic hormone (ACTH) plasma levels evaluated by radioimmunoassay. There was evidence of lymphocytic infiltration of the adrenal glands, which however, was not accompanied by changes in corticosterone levels. There was a reduction in ACTH levels with age (R 2 = 0.98). Mice from other strains (TFW, CBA and Balb/c) showed no lymphocytic infiltration in the adrenal glands and had lower levels of corticosterone than NOD mice of similar ages, but the differences were not significant. In conclusion, since the NOD mouse shows histological signs of adrenalitis, thyroiditis, sialitis and parathyroiditis, this animal can be regarded as a model to investigate mechanisms involved in diffuse lymphocytic infiltration of peripheral endocrine glands (polyendocrine autoimmunity). In addition, if diabetes in the NOD mouse is the result of a polyendocrine disorder rather than a process specific for diabetes, then this finding may have implications for attempts to prevent type-1 diabetes in humans.