Corticosteroid Stress Response Research Articles

Chronic cortisol stimulation enhances hypothalamus-specific enrichment of metabolites in the rainbow trout brain.

The hypothalamus is a key integrating center that is involved in the initiation of the corticosteroid stress response, and in regulating nutrient homeostasis. Although cortisol, the principal glucocorticoid in humans and teleosts, plays a central role in feeding regulation, the mechanisms are far from clear. We tested the hypothesis that the metabolic changes to cortisol exposure signal an energy excess in the hypothalamus, leading to feeding suppression during stress in fish. Rainbow trout (Oncorhynchus mykiss) were administered a slow-release cortisol implant for 3 days, and the metabolite profiles in the plasma, hypothalamus, and the rest of the brain were assessed. Also, U-13C-glucose was injected into the hypothalamus by intracerebroventricular (ICV) route, and the metabolic fate of this energy substrate was followed in the brain regions by metabolomics. Chronic cortisol treatment reduced feed intake, and this corresponded with a downregulation of the orexigenic gene agrp, and an upregulation of the anorexigenic gene cart in the hypothalamus. The U-13C-glucose-mediated metabolite profiling indicated an enhancement of glycolytic flux and tricarboxylic acid intermediates in the rest of the brain compared with the hypothalamus. There was no effect of cortisol treatment on the phosphorylation status of AMPK or mechanistic target of rapamycin in the brain, whereas several endogenous metabolites, including leucine, citrate, and lactate were enriched in the hypothalamus, suggesting a tissue-specific metabolic shift in response to cortisol stimulation. Altogether, our results suggest that the hypothalamus-specific enrichment of leucine and the metabolic fate of this amino acid, including the generation of lipid intermediates, contribute to cortisol-mediated feeding suppression in fish.NEW & NOTEWORTHY Elevated cortisol levels during stress suppress feed intake in animals. We tested whether the feed suppression is associated with cortisol-mediated alteration in hypothalamus metabolism. The brain metabolome revealed a hypothalamus-specific metabolite profile suggesting nutrient excess. Specifically, we noted the enrichment of leucine and citrate in the hypothalamus, and the upregulation of pathways involved in leucine metabolism and fatty acid synthesis. This cortisol-mediated energy substrate repartitioning may modulate the feeding/satiety centers leading to the feeding suppression.

Sustained action of developmental ethanol exposure on the cortisol response to stress in zebrafish larvae and adults.

BackgroundEthanol exposure during pregnancy is one of the leading causes of preventable birth defects, leading to a range of symptoms collectively known as fetal alcohol spectrum disorder. More moderate levels of prenatal ethanol exposure lead to a range of behavioural deficits including aggression, poor social interaction, poor cognitive performance and increased likelihood of addiction in later life. Current theories suggest that adaptation in the hypothalamo-pituitary-adrenal (HPA) axis and neuroendocrine systems contributes to mood alterations underlying behavioural deficits and vulnerability to addiction. In using zebrafish (Danio rerio), the aim is to determine whether developmental ethanol exposure provokes changes in the hypothalamo-pituitary-interrenal (HPI) axis (the teleost equivalent of the HPA), as it does in mammalian models, therefore opening the possibilities of using zebrafish to elucidate the mechanisms involved, and to test novel therapeutics to alleviate deleterious symptoms.Results and ConclusionsThe results showed that developmental exposure to ambient ethanol, 20mM-50mM 1-9 days post fertilisation, had immediate effects on the HPI, markedly reducing the cortisol response to air exposure stress, as measured by whole body cortisol content. This effect was sustained in adults 6 months later. Morphology, growth and locomotor activity of the animals were unaffected, suggesting a specific action of ethanol on the HPI. In this respect the data are consistent with mammalian results, although they contrast with the higher corticosteroid stress response reported in rats after developmental ethanol exposure. The mechanisms that underlie the specific sensitivity of the HPI to ethanol require elucidation.

Atrazine and its degradates have little effect on the corticosteroid stress response in the zebrafish

The present study examined the effects of atrazine on basal and forced swimming induced changes in whole body cortisol content in adult zebrafish. Zebrafish were exposed to graded concentrations of atrazine or the atrazine degradates deisopropylatrazine (DIA), deethylatrazine (DEA) and diamino-s-chlorotriazine (DACT) for up to 10days. Some fish were sampled for the measurement of whole body cortisol levels under basal conditions while others were sampled after being subjected to a 20min swimming challenge in order to quantify stress induced cortisol levels. In one experiment, zebrafish were subjected to two bouts of forced swimming 3h apart to test whether prior atrazine exposure affects the ability of the fish to respond appropriately to a repeated stressor. The results demonstrated that controls not exposed to atrazine and zebrafish exposed to atrazine or the atrazine degradates at nominal concentrations of up to 100μg/L consistently exhibited increased whole body cortisol content in response to the swimming challenge. Separate analyses revealed few changes in basal or stress induced cortisol levels following atrazine exposure. Overall, these data suggest that atrazine and some of its degradates at the concentrations tested have minimal effects on the cortisol mediated stress response in the zebrafish.

Early adversity and serotonin transporter genotype interact with hippocampal glucocorticoid receptor mRNA expression, corticosterone, and behavior in adult male rats.

Despite its importance for development, relatively little is known about how allelic variation interacts with both pre- and postnatal stress. We examined the interaction between serotonin transporter (5-HTT) genotype, prenatal and postnatal stress on glucocorticoid receptor (GR) mRNA expression, corticosteroid stress responses, and behavior in adult male rats. Prenatal stress involved a daily restraint of pregnant dams from gestational Day 10-21. Postnatal stress involved raising pups after parturition either by their mothers (MR) or in the artificial rearing (AR) paradigm, with or without additional "licking-like" stroking stimulation. 5-HTT genotype, hippocampal GR mRNA level, corticosteroid stress response, and behaviors including startle response, prepulse inhibition (PPI), and locomotor activity were measured in adult male rat offspring. We found significant genotype by prenatal stress interactions for hippocampal GR mRNA levels and for the corticosterone stress responses in adulthood. In contrast, behavioral endpoints tended to be more clearly affected by an interaction between genotype and postnatal environment. These findings suggest that allelic variation in the 5-HTT gene interacts with the prenatal environment to affect the hypothalamic-pituitary-adrenal (HPA) axis physiology and the postnatal environment to affect behavior. These results are the first to indicate a role for genetic variation in the 5-HTT gene in physiology and behavior in the rat.

Whole-body corticosteroid and plasma cortisol concentrations in larval and juvenile Atlantic cod Gadus morhua L. following acute stress

Methods were developed to assess whole-body immunoreactive corticosteroid concentrations (IRC) and plasma levels of cortisol in Atlantic cod subjected to several common, acute stressors. A measurable corticosteroid stress response was observed at the first sampling in whole bodies of 8-day post-hatch (dph) larvae. Two groups of juveniles (∼5 and 30 g) were subjected to a 30 s net stressor and whole-body IRC and plasma cortisol levels were determined. Post-stressor IRC in smaller fish rose approximately 14-fold, peaked at 1 h, were sustained for 3–6 h and returned to pre-stressor levels within 24 h. Post-stressor plasma cortisol levels in larger fish rose approximately 18-fold, peaked at 0.5–1 h, were sustained for 1–3 h and then returned to near pre-stressor levels after 24 h. Immunoreactive corticosteroid concentrations appeared to remain elevated longer than plasma cortisol levels suggesting that steroids other than cortisol were contributing to total immunoreactivity in homogenates. Juveniles exposed to either a grading procedure or high density transport had maximal IRC and plasma cortisol levels within 90 min which returned to pre-stressor levels within 24–72 h. A reduction in water salinity (20 g L−1) did not moderate the corticosteroid response in juveniles. The results show that Atlantic cod respond to common, acute stressors in a manner similar to other teleosts. Whole-body homogenates can be used to identify changes in IRC in response to acute stress in cod with the caveat that recovery IRC may differ from plasma cortisol concentrations.

Reproduction elevates the corticosterone stress response in common fruit bats

Changes in reproductive state or the environment may affect the sensitivity of the hypothalamic-pituitary-andrenal (HPA) axis. However, little is known about the dynamics of the resulting corticosteroid stress response, in particular in tropical mammals. In this study, we address the modulation of corticosterone release in response to different reproductive conditions and seasonality in 326 free-living common fruit-eating bats (Artibeus jamaicensis) on Barro Colorado Island in Panama during dry and wet seasons. We present strong evidence that stress sensitivity is primarily modulated by reproductive condition. In reproductively active females, corticosterone increases were more rapid and reached higher levels, but also decreased significantly faster than in inactive females. The corticosterone response was weaker in reproducing males than in females and delayed compared to non-reproductive males. Testes volume in reproductively active males was negatively correlated with corticosterone concentrations. Our findings suggest differentiated dynamics in the corticosterone stress response between sexes, potentially reflecting conflicting ecological demands. In females, a strong acute corticosterone response may represent high stress- and risk-sensitivity that facilitates escape and thus helps to protect reproduction. In males, suppression during reproductive activity could reflect lowered stress sensitivity to avoid chronically elevated corticosterone levels in times of frequent aggressive and therefore costly inter-male encounters.

European eels, Anguilla anguilla (L.), infected with Anguillicola crassus exhibit a more pronounced stress response to severe hypoxia than uninfected eels

The parasite, Anguillicola crassus is a non-native species that infects naive European eels, Anguilla anguilla, and causes pathological damage to the swimbladder, potentially compromising their ability to cope with hypoxic conditions. This study aimed to elucidate whether anguillicolosis exacerbates the stress responses to exposure to hypoxic water, conditions that have been implicated in mass mortalities of wild infected European eels. Blood parameters in infected and uninfected eels were measured during exposure to severe hypoxia over an 8-h period. Infected fish showed significantly higher levels of plasma cortisol compared with uninfected eels after 4 h of hypoxia. Uninfected fish showed an almost twofold increase in plasma glucose after 8-h exposure to hypoxia but infected fish showed no significant change, so that the plasma glucose concentration was significantly higher in uninfected eels than in infected eels. Both groups showed similar elevations in blood haematocrit, suggesting a similar catecholamine response in infected and uninfected eels. The lack of a hyperglycaemic response in infected eels, despite indirect evidence of a catecholamine response to hypoxia, may reflect an increase in glucose turnover. The data suggest that anguillicolosis results in a significantly greater corticosteroid stress response to hypoxia accompanied by a higher metabolic cost.

Molecular mimicry of ACTH in SARS ? implications for corticosteroid treatment and prophylaxis

For a virus to survive and replicate in an organism, it must employ strategies to evade and misdirect the host's immune response. There is compelling evidence that the primary immunoevasive strategy utilized by the SARS virus, like influenza, is to inhibit its host's corticosteroid stress response. This is accomplished by viral expression of amino acid sequences that are molecular mimics of the host's adrenocorticotropin hormone (ACTH). When the host produces antibodies against these viral antigens, the antibodies also bind to the host's own ACTH, which limits the host's stress response by interfering with ACTH's ability to stimulate the secretion of corticosteroids. This inadequate corticosteroid response provokes symptoms as a result of a relative adrenocortical insufficiency. Treatment with corticosteroids can relieve the patient's symptoms of adrenocortical insufficiency and give them the corticosteroid levels needed to fight their infection. Similarly, by taking moderate daily doses of corticosteroids as a prophylactic, it may be possible to avoid clinical infection with SARS. If SARS's ACTH mimic strategy never has an opportunity to get started, SARS's ability to evade its host's immune system while its viral load is low will be significantly impaired. In this article, amino acid sequences from the SARS and influenza viruses representing likely homology to human ACTH are identified. Evidence demonstrating that ACTH autoantibodies are produced during influenza infection is also presented. Early treatment with corticosteroids should lower the dose necessary to counteract SARS's ACTH autoantibody mechanism. If corticosteroid treatment is delayed until inflammatory cytokine levels are causing serious injury, only high doses of corticosteroids are likely to be effective.

Molecular mimicry of ACTH in SARS – implications for corticosteroid treatment and prophylaxis

For a virus to survive and replicate in an organism, it must employ strategies to evade and misdirect the host's immune response. There is compelling evidence that the primary immunoevasive strategy utilized by the SARS virus, like influenza, is to inhibit its host's corticosteroid stress response. This is accomplished by viral expression of amino acid sequences that are molecular mimics of the host's adrenocorticotropin hormone (ACTH). When the host produces antibodies against these viral antigens, the antibodies also bind to the host's own ACTH, which limits the host's stress response by interfering with ACTH's ability to stimulate the secretion of corticosteroids. This inadequate corticosteroid response provokes symptoms as a result of a relative adrenocortical insufficiency. Treatment with corticosteroids can relieve the patient's symptoms of adrenocortical insufficiency and give them the corticosteroid levels needed to fight their infection. Similarly, by taking moderate daily doses of corticosteroids as a prophylactic, it may be possible to avoid clinical infection with SARS. If SARS's ACTH mimic strategy never has an opportunity to get started, SARS's ability to evade its host's immune system while its viral load is low will be significantly impaired. In this article, amino acid sequences from the SARS and influenza viruses representing likely homology to human ACTH are identified. Evidence demonstrating that ACTH autoantibodies are produced during influenza infection is also presented. Early treatment with corticosteroids should lower the dose necessary to counteract SARS's ACTH autoantibody mechanism. If corticosteroid treatment is delayed until inflammatory cytokine levels are causing serious injury, only high doses of corticosteroids are likely to be effective.

THE STRESS RESPONSE OF EUROPEAN STONECHATS DEPENDS ON THE TYPE OF STRESSOR

Abstract The acute increase in plasma levels of corticosteroid hormones in response to a stressful situation is essential for adequate physiological and behavioural responses to unpredictable events. The pattern and amplitude of the corticosteroid stress response has been extensively studied to compare endocrine adaptations between different life history stages, but also to determine environmental and physiological disturbances. Most studies on birds have used a simple and repeatable standardized stress-protocol. After capture, blood samples are taken at fixed time intervals from the bird kept in a cloth bag. Capture and handling during this procedure are stressful events which typically result in enhanced secretion of corticosterone. However, it is not known whether the stress response obtained with the cloth bag protocol is comparable with a life-threatening situation such as the confrontation with a predator. In this study, we investigated the plasticity of the stress-response towards different stimuli. We compared the stress responses of European stonechats (Saxicola torquata rubicola) exposed to different stressors: (1) a standard cloth bag; (2) space restraint by caging; and (3) caging and additional confrontation with a live predator, a tawny owl (Strix aluco). Our results show that the stress response induced by the predator was greater and the stress response induced by the cage tended to be greater than that induced by the cloth bag protocol. Thus, the present study showed that the stress response may vary depending on the type of stressor.

In Vitro Effects of ACTH on Interrenal Corticosteroidogenesis during Early Larval Development in Rainbow Trout

Interrenal tissue from embryonic and larval rainbow trout (Oncorhynchus mykiss) was cultured in vitro and exposed to various doses of adrenocorticotropin (ACTII) to document the ontogeny of interrenal responsiveness to tropic stimulation. Resting and acute stress-induced in wholebody cortisol levels in vivo were also measured to determine if the corticosteroid stress response first develops with the onset of interrenal responsiveness to ACTH. No evidence was found that the hypothalamic-pituitary-interrenal (HPI) axis of rainbow trout is transiently activated prior to hatching. In vivo, a corticosteroid stress response was first observed 2 weeks after hatching, and stress-induced cortisol levels (at 1 hr poststress) were significantly higher 3 weeks after hatching than they were at 2 or 4 weeks after hatching. In contrast, cultured interrenal tissue produced significant levels of cortisol in response to ACTH at the time of hatching, and in vitro cortisol production by the interrenal increased significantly between 3 and 4 weeks after hatching. Interrenal sensitivity to ACTH did not change appreciably with development. We conclude that (1) the final maturation of the corticosteroid stress response in rainbow trout occurs at the level of the brain and/or sensory inputs and not at the level of the interrenal cell; (2) negative feedback mechanisms within the HPI axis develop 3 to 4 weeks after hatching; and (3) the period between 3 and 4 weeks after hatching may be homologous to the stress hyporesponsive period after birth in mammals and thus could be a stage when environmental influences can permanently alter the development of the corticosteroid stress response in rainbow trout.

Indices of stress in rats: Effects of sex, perinatal alcohol and artificial rearing

Three groups of rats were normally reared by dams, artificially reared but not exposed to alcohol or artificially reared and exposed to 6.6 g/kg/day of ethanol condensed into 8 h of each 24-h period. Alcohol exposure was given from postnatal day 4 through 9 and artificial rearing was conducted from postnatal day 4 to 12. In adulthood, approximately half of the rats were fitted with a chronic jugular catheter and were exposed to swim stress for 1 min in 21°C water. Alcohol exposure augmented the corticosteroid stress response to the swim stress in female rats but not in male rats. The other half of the animals were tested for acquisition and extinction of a conditioned emotional response (CER). While alcohol exposure had no effects on the CER, extinction of CER was greatly accelerated by artificial rearing alone in female rats but not in male rats. Taken together, these findings suggest that some aspects of the stress response in female rats are more vulnerable to insults during the early postnatal period than those in male rats and that the insult-induced alterations can affect hormonal and behavioral measures differentially.

Inhibition of infant glucocorticoid stress response: Specific role of maternal cues

Previous work from this laboratory has shown that passive contact with an anesthetized lactating dam eliminates the corticosteroid stress response to novelty in 12-, 16-, and 20-day-old rat pups. In the present study, we further examined some of the sensory and developmental aspects of this phenomenon. In two experiments, we asked whether inhibition of the corticosteroid stress response is related exclusively to contact with a maternal stimulus as opposed to other social stimuli. Experiment I compared the effectiveness of contact with an anesthetized dam vs, an anesthetized adult male rat. At 12 and 16 days of age, contact with an adult male was somewhat effective in reducing stress responsiveness, whereas at 20 days, contact with an adult male was entirely ineffective. At all ages, contact with an anesthetized dam was an effective inhibitor of the stress response. Experiment II compared the relative effectiveness of contact with an anesthetized dam vs. an anesthetized sibling pup. At all ages, contact with a dam was very effective, whereas contact with an anesthetized pup was entirely ineffective in inhibiting the glucocorticoid stress response. In Experiment III, the effect of maternal contact was assessed during a period of development when the biological, and presumably social, significance of the lactating-dam stimulus is changing. In this study, 20-, 24-, and 28-day-old rat pups revealed a progressive decrement in the ability of maternal contact to inhibit stress responsiveness. These findings replicate and extend our previous ones by showing that maternal stimuli play a special role in the modulation of pituitary-adrenal activity during development.

Plasma cortisol and secondary stress responses of cultured red drum ( Sciaenops ocellatus) to several transportation procedures

Transportation procedures induced rapid elevations in plasma cortisol and glucose concentrations (100–160 ng/ml and 60–140 mg/100 ml, respectively) within 15–30 min of capture and loading in cultured juvenile red drum. The elevations were transient and plasma levels of cortisol returned to baseline levels during the 5.5 h transport, suggesting that capture and loading are the most traumatic procedures. Plasma glucose concentrations had returned to baseline values within 1–2 days of transport. Plasma osmolality increased during transportation in 32 ppt seawater and decreased during transport in 4 ppt seawater. Survival ranged from 96 to 100%, indicating that despite the trauma associated with initial transport procedures, juvenile red drum can be transported successfully in seawater or low salinity seawater. Anesthesia with MS-222 (80 mg/l) prior to capture, coupled with the use of sedating doses (5 and 25 mg/l MS-222) in the transport tanks, did not decrease the magnitude of the stress responses. On the contrary, the corticosteroid stress response was augmented in fish transported in 25 mg/l MS-222. Laboratory tests showed that long-term (30–90 min) exposure to sedating doses of the anesthetic caused a dose-dependent increase in plasma cortisol levels, whereas anesthetization of red drum with MS-222 prior to capture and transport in anesthetic-free seawater markedly reduced the plasma corticosteroid response after capture/loading and at the end of transport. Plasma glucose levels and osmolality were also lower in those fish anesthetized prior to capture. These results suggest that acute exposure to immobilizing doses of an anesthetic, MS-222, is an effective method of reducing endocrine and metabolic disturbances during transportation of red drum.

Plasma Corticosteroid Stress Response of Fourteen Species of Warmwater Fish to Transportation

Plasma corticosteroid concentrations were measured in 14 species of fish immediately after they were electrofished from reservoirs on the Alabama River and after they had been transported for 2 h. There was no corticosteroid response in spotted gars Lepisosteus oculatus. Bowfins Amia calva, longnose gars Lepisosteus osseus, and freshwater drums Aplodinotus grunniens had only small corticosteroid increases (14–39 ng/mL) during transportation. Corticosteroids increased by intermediate amounts (59–184 ng/mL) during transportation in blue catfish Ictalurus furcatus, paddlefish Polyodon spathula, largemouth bass Micropterus salmoides, channel catfish Ictalurus punctatus, river carpsuckers Carpiodes carpio, white bass Morone chrysops, striped bass Morone saxatilis, and crappies Pomoxis sp. The greatest increases were 223 ng/mL in gizzard shad Dorosoma cepedianum and 286 ng/mL in common carp Cyprinus carpio. Spotted and longnose gars, largemouth bass, and common carp also were held in tanks for about 2 months at 21°C and then stressed by confinement in a dip net for 30 min. The confinement caused significant increases (P < 0.01) of plasma corticosteroid concentration in all four species. Dip-net confinement appears to be a useful method for comparing corticosteroid responses among species of warmwater fish.

Serotonin in the development of pituitary-adrenocortical response to stress

Adrenocortical response to intraperitoneal 5-HT administration and immobilization stress is observed in rats as early as the 4th day of life when response to intraventricular administration is still absent. Dexamethasone pretreatment influences plasma cortico-steroid response to stimulation of peripheral 5-HT receptors in adult rats but does not alter such response to intraperitoneal 5-HT administration and immobilization in 4-day-old rats. Plasma 11-OHCS response to this stress increases considerably by days 12–16, when stress-induced changes in brain 5-HIAA are also observed. The increase of adrenocortical response to stress coincides with the appearance of brain 5-HT metabolic stress-induced changes as well as pituitary-adrenocortical response to centrally administered 5-HT. Corticosteroid stress response in neonate rats may be due, at least partially, to stimulation of peripheral 5-HT receptors, rather than to brain 5-HT, the latter appearing to become essential for the pituitary-adrenocortical system response to this stress from days 12–16 of life.

A general procedure for estimation of corticosteroid response in individual rats

A procedure is presented whereby microliter volumes of plasma, obtained rapidly and repeatedly from the tail vein of unanestheti zed rats, can be analyzed for corticosterone. Preliminary results suggest that (I) basal levels are considerably lower and (2) the latency to corticosteroid stress response is shorter than previously reported.

Corticosteroid Concentrations in Sockeye Salmon (Oncorhynchus nerka) Exposed to Low Concentrations of Copper

Yearling sockeye salmon (Oncorhynchus nerka) were exposed for 1–24 h to 10−7, 10−6, or 10−5 molar cupric sulphate in freshwater aquaria. Plasma cortisol, cortisone, and "total" corticosteroid concentrations were measured by a competitive protein binding technique.Cortisol, cortisone and "total" corticosteroid levels were significantly higher than control concentrations after 1 h of exposure to 10−5 or 10−6 M copper. "Total" corticosteroid and cortisone concentrations were significantly higher than control concentrations after 2 and 4 h of exposure to 10−7 M copper, respectively. Fish exposed to 10−5 M copper died between 8 and 24 h.The data reflect a rapid corticosteroid stress response to lethal and sublethal concentrations of copper. The technique may be of use for rapid evaluation of effluents containing heavy metals, especially those containing a mixture of toxicants.

Thoracic lymph duct cannulation of mice infected with lymphocytic choriomeningitis (LCM) and ectromelia viruses.

WEHI mice infected with LCM virus or with the virulent Hampstead mouse strain of ectromelia virus showed a decrease in the output of small lymphocytes from the thoracic duct. These infections were lethal, and caused thymic cortex depletion and fatty liver changes which were especially severe in the case of LCM virus infection. These changes were due to an adrenal-cortex mediated response. The fall in cell output from thoracic lymph could be attributed to the combined effects of the destruction of infected splenic and lymph node lymphocytes, and lymphocyte-destruction mediated by the corticosteroid stress response to infection.

Infantile Stimulation and Adult Stature of Human Males1

physiological effects. One of the more persistent.and striking of these effects, an increase in rate of growth and size attained at adulthood, is of particular relevance to this paper. It has been summarized by Levine (1960:85), one of the leading researchers in the field, as follows: "In all respects, in fact, the manipulated infants exhibit a more rapid rate of development. They open their eyes earlier and achieve motor coordination sooner. Their body hair grows faster, and they tend to be significantly heavier at weaning. They continue to gain weight more rapidly than the nonstimulated animals even after the course of stimulation has been completed at three weeks of age. Their more vigorous growth does not seem to be related to food intake but to better utilization of the food consumed and probably to a higher output of the somatotrophic (growth) hormone from the pituitary." As will be discussed below, it seems reasonable to interpret these unusual early experiences as stressful to the immature animals. Although the exact mechanism underlying the stimulating effects of these early experiences upon growth has not been established, it is known that a lasting change in the endocrine system does occur. Since growth is presumably inhibited by corticosteroid stress response hormones, one might hypothe