Pituitary Adrenals Research Articles

Evaluation of therapeutic effects of aqueous cinnamon extract against obesity associated dysregulation of pituitary-adrenal axis

Obesity is distinguished by unwanted and surplus accumulation of lipids in body principally in adipocytes. Inactive lifestyle and dietary irregularities are considered as premiers among a variety of obesogenic risk factors. Obesity is associated with variations in the concentration of trophic and tropic hormones from pituitary gland affecting different body parts and other endocrine glands including adrenal gland. Current study was design to explore the anti-obesity potential of cinnamon (Cinnamomum verum) against high sugar and high fat induced hyper-activity of pituitary-adrenal (PA) axis and obesity. Twenty-five healthy Wistar albino female rats were selected as model animal. Body weight, oral glucose tolerance test, serum cortisol, hematology and histopathological analysis were performed. The high sugar and high fat induced increase in body eight was decline by cinnamon administration. Hematological analysis revealed a significant decreased concentration of RBCs and hemoglobin and increased WBCs and platelet count following sub-acute exposure of high sugar and high fat changes were attenuated by cinnamon. High sugar and fat associated elevated serum cortisol was normalized after cinnamon exposure. Moreover, cinnamon protected the histopathological alterations following high sugar and fat administration, showed protective effects of Cinnamon against obesity associated dysregulation of PA axis and metabolic impairment.

Physiological and behavioural consequences of long-term moderate treadmill exercise

The benefits of long-term moderate exercise for health are widely accepted in humans, but few animal studies have been undertaken to characterize the effects of such activity on emotionality and responsiveness to stress. The present study describes the effects of long-term moderate forced treadmill training (36 weeks) on exploratory activity, anxiety-like behaviour, and the resting or stress levels of some physiological variables, including pituitary-adrenal (PA) hormones. Five-week-old male Sprague-Dawley rats were trained on the treadmill (TM) for 36 weeks, using a more moderate training (12m/min, 30min/day, 4-5 days/week) than that currently used in the literature. Two groups were used as controls: a non-handled sedentary (SED) group, receiving no manipulation, and a control (CON) group exposed to a stationary treadmill for the same amount of time as the TM group. In accordance with literature data, TM rats showed lower resting levels of glucose, triglycerides and cholesterol than the other two groups. The TM and CON groups both showed higher ambulation than the SED group in some behavioural tests, without evidence for altered anxiety. Resting levels of adrenocorticotropin (ACTH) and corticosterone did not differ among the groups, but a reduced ACTH response to both a novel environment (mild stressor) and an active escape-avoidance task (severe stressor) was observed in TM rats, whereas changes in corticosterone were modest. The results support the view that the physiological consequences of long-term moderate training are beneficial, including reduced PA responsiveness to stress, even though exercise training did not affect anxiety-like behaviour.

Pregnancy reduces the responsiveness of the pituitary–adrenal axis to dexamethasone

This study aimed to examine the influence of pregnancy on responsiveness of the pituitary–adrenal (PA) axis to dexamethasone (Dx) in rats. Dams and virgins were injected with Dx in three consecutive daily doses of 1.0, 0.5, 0.5mg/kg/bw, starting from day 16 of pregnancy, and sacrificed 24 and 72h after termination of treatment. Immunocytochemical, morphometrical and biochemical methods were used to assess pituitary and adrenal function. Three-way ANOVA revealed Dx inhibition of the PA axis in virgin and pregnant females after 24 and 72h. Pregnant females demonstrated a significantly lower (p<0.05) degree of suppression regarding ACTH volume density and blood concentrations and the volume and number of the zona fasciculata and zona reticularis cells, comparing with virgin females 72h following Dx administration, accompanied by total recovery of the zona glomerulosa. In contrast to virgin females, the corticosterone levels on day 21 of gestation reached control levels. Between days 19 and 21 of pregnancy, a significant increase in estrogen levels and the fall of progesterone influence, at least partially, the presented differences. It can be concluded that the PA axis response to the inhibitory influence of Dx is less pronounced in gravid females during late pregnancy than in virgin rats.

Cat odor causes long-lasting contextual fear conditioning and increased pituitary-adrenal activation, without modifying anxiety

A single exposure to a cat or cat odors has been reported by some groups to induce contextual and auditory fear conditioning and long-lasting changes in anxiety-like behaviour, but there is no evidence for parallel changes in biological stress markers. In the present study we demonstrated in male rats that exposure to a novel environment containing a cloth impregnated with cat fur odor resulted in avoidance of the odor, lower levels of activity and higher pituitary-adrenal (PA) response as compared to those exposed to the novel environment containing a clean cloth, suggesting increased levels of stress in the former animals. When re-exposed 9 days later to the same environment with a clean cloth, previously cat fur exposed rats again showed avoidance of the cloth area and lower levels of activity, suggesting development of contextual fear conditioning, which again was associated with a higher PA activation. In contrast, unaltered both anxiety-like behaviour and PA responsiveness to an elevated plus-maze were found 7 days after cat odor exposure. It is concluded that: (i) PA activation is able to reflect both the stressful properties of cat fur odor and odor-induced contextual fear conditioning; (ii) development of cat odor-induced contextual fear conditioning is independent of the induction of long-lasting changes in anxiety-like behaviour; and (iii) greater PA activation during exposure to the odor context is not explained by non-specific sensitization of the PA axis caused by previous exposure to cat fur odor.

Pituitary–adrenal responses to arm versus leg exercise in untrained man

The purpose of this study was to examine pituitary-adrenal (PA) hormone responses [beta-endorphin (beta-END), adrenocorticotropic hormone (ACTH) and cortisol] to arm exercise (AE) and leg exercise (LE) at 60 and 80% of the muscle-group specific VO2 peak. Eight healthy untrained men (AE VO2 peak=32.4+/-3.0 ml kg(-1) min(-1), LE VO2 peak=46.9+/-5.3 ml kg(-1) min(-1)) performed two sub-maximal AE and LE tests in random order. Plasma beta-END, ACTH and cortisol were not different (P>0.05) between AE and LE at either exercise intensity; the 60% testing elicited no changes from pre-exercise (PRE) values. For 80% testing, plasma beta-END, ACTH and cortisol were consistently, but not significantly, greater during LE than AE. In general, plasma beta-END and ACTH were higher (P<0.05) during 80% exercise, than PRE, for both AE and LE. Plasma cortisol was elevated (P<0.05) above PRE during 80% LE, and following 80% for both AE and LE. Plasma ACTH was higher (P<0.05) during 80% LE and AE versus 60% LE and AE, respectively. Plasma beta-END and cortisol were significantly higher during and immediately after 80% LE than 60% LE. Thus, plasma beta-END, ACTH and cortisol responses were similar for AE and LE at the two relative exercise intensities, with the intensity threshold occurring somewhere between 60 and 80% of VO2 peak. It appears that the smaller muscle mass associated with AE was sufficient to stimulate these PA axis hormones in a manner similar to LE, despite the higher metabolic stress (i.e., plasma La-) associated with LE.

BASAL GLUCOCORTICOID ACTIVITY DECREASES WITH TRAINING AND CORRELATES NEGATIVELY WITH MUSCLE CYTOCHROME C OXIDASE ACTIVITY

High pituitary-adrenal (PA) activity is associated with a number of disorders including obesity and diabetes. In addition, high levels of plasma glucocorticoids (GCs) appear to decrease skeletal muscle mass, whereas the effects on mitochondrial function and content are ambiguous. PURPOSE 1) to examine the adaptive responses of basal PA activity to endurance training in rats, and 2) to determine if basal GC levels correlate with muscle cytochrome c oxidase (COX) activity in trained rats. METHODS Male Sprague-Dawley rats either remained sedentary or were swim trained 45-min/day, 5 days/wk for 2, 4, or 6 wks (n = 8–10/group). Sedentary rats were placed in shallow water for same duration but did not swim. One day after the last treatment bout, rats were decapitated (10AM) and plasma and tissue samples were collected to analyze basal plasma ACTH and corticosterone (CORT) levels and muscle COX activity. RESULTS Basal CORT levels increased from 40.1 ± 8.2ng/mL (X ± SEM) at 2wks to 88.3 ± 30.7ng/ml at 6 wks in sedentary rats (p = 0.05). In trained rats, levels increased (p < 0.05) by 4wks then declined toward pre-training levels by 6 wks (2wk:25.9 ± 6.1, 4wk:51.0 ± 5.0, 6wk:37.0 ± 8.3 ng/mL). By 6 wks, CORT levels were 42% lower in trained compared to sedentary rats. ACTH levels followed a similar trend as CORT in both groups. COX activity in red rectus femoris did not change in sedentary rats during the 6 wks (7.29 ± 0.17U/gm muscle,n = 8/group) but increased in trained rats from 8.74 ± 0.54 U/gm muscle before training to 12.0 ± 0.80 U/gm muscle at 6wks (p < 0.01). Mean COX activity for 2, 4 and 6 wk training groups correlated with mean basal CORT levels (r = −0.88, p < 0.05). CONCLUSION Our results suggest that training is associated with an attenuation in basal PA activity which, in turn, is associated with increases in muscle mitochondrial content. Thus, one mechanism by which endurance training can improve muscle mitochondrial metabolism may be through a lowering of basal plasma GCs.

Dynamics of the pituitary-adrenal ensemble in hypocretin-deficient narcoleptic humans: blunted basal adrenocorticotropin release and evidence for normal time-keeping by the master pacemaker.

Narcolepsy is a sleep disorder caused by disruption of hypocretin (orexin) neurotransmission. It has been suggested that anomalous timing by the biological clock contributes to the symptomatology. Hypocretins stimulate the pituitary-adrenal (PA) axis in rodents. We explored whether hypocretin deficiency disrupts circadian timing and blunts PA hormone release. We deconvolved 24-h plasma profiles of ACTH and cortisol, and determined their circadian rhythm by cosinor analysis in seven hypocretin-deficient narcoleptic males and seven matched controls. Basal and total ACTH production were blunted in narcoleptics [310 +/- 86 vs. 760 +/-160 ng/liter.24 h (P = 0.02) and 920 +/- 147 vs. 1460 +/- 220 ng/liter.24 h (P = 0.04), respectively], whereas pulsatile release did not differ between groups. In contrast, basal, pulsatile and total cortisol secretion were similar in both groups. The cross-approximate entropy of the joint ACTH/cortisol time series was higher in narcoleptics (1.26 +/- 0.07 vs. 1.07 +/- 0.04; P = 0.04), reflecting reduced secretory process regularity. The acrophases of both ACTH and cortisol occurred at similar clock times (approximately 0830 h) in patients and controls, which supports the idea that the master pacemaker is intact in narcolepsy. The reduced (basal) ACTH secretion and the diminished secretory process regularity of the ACTH/cortisol ensemble conjointly suggest that hypocretin deficiency induces changes in the interplay between PA hormones.

Pituitary-adrenal function following dexamethasone-cyclophosphamide pulse therapy for pemphigus.

Systemic corticosteroid therapy is known to lead to pituitary-adrenal (PA) suppression. Although patients treated for pemphigus with dexamethasone-cyclophosphamide pulse (DCP) therapy have shown no evidence of PA suppression, no study has been conducted to study this possible side-effect of DCP therapy. To study the effect of DCP therapy for pemphigus on PA function. A cross-sectional study was carried out in 33 patients who completed phase II of DCP therapy in a single centre, a large teaching hospital in New Delhi, India. Serum cortisol levels following adrenocorticotrophic hormone stimulation were analysed in 31 patients. Seventeen (55%) patients showed suppressed PA function. Suppressed function occurred more frequently in patients who had received pulses of dexamethasone in addition to DCP therapy in the first phase of treatment (P = 0.055). Suppressed PA function occurs in about half of patients who receive DCP therapy for pemphigus. These patients probably do not require routine replacement therapy with corticosteroids but may need supplementation during periods of stress.

Effects of acute alcohol intoxication on pituitary-gonadal axis hormones, pituitary-adrenal axis hormones, β-endorphin and prolactin in human adolescents of both sexes

Teenage drinking continues to be a major problem in industrialized countries, where almost 35% of alcohol drinkers are under 16 years old. In the present paper we studied the effects of acute alcohol intoxication (AAI) on the pituitary-gonadal (PG) axis hormones, and the possible contribution of pituitary-adrenal (PA) axis hormones, β-endorphin (BEND), and prolactin (PRL) to the alcohol-induced dysfunction of PG axis hormones. Blood samples were drawn from adolescents that arrived at the emergency department with evident behavioral symptoms of drunkenness (AAI) or with nil consumption of alcohol (controls [C]). Our results demonstrated that AAI produces in adolescents a high increase in plasma PRL, ACTH, and cortisol (F), and a contradictory behavior of testosterone (T) according to gender: plasma T was increased in females and decreased in males. ACTH and PRL correlated positively with F, dehydroepiandrosterone-sulphate (DHEAS) and T in females, which suggests that PRL and ACTH could synergistically stimulate adrenal androgen production. In contrast, the decrease in T and increase in BEND in males suggests that AAI could have an inhibitory effect on testicular T, perhaps mediated by BEND. The hormones studied are involved in the development of secondary sexual characteristics and the growth axis during adolescence. The deleterious effects of alcohol abuse should be made known to adolescents and the appropriate authorities.

The effect of chronic administration of antidepressants on the circadian pattern of corticosterone in the rat.

Although antidepressant administration has been reported to alter the pituitary adrenal (PA) axis, the results are puzzling. In the present work, two possible factors contributing to these contradictory results were studied in adult male Sprague-Dawley rats: (i) the type of antidepressant and (ii) the time of day at which samples were taken. Samples were taken under nonstressful conditions. In expt 1, the acute effects of two doses (10 and 20 mg/kg) of the tricyclics clomipramine (CMI), desipramine (DMI) and imipramine (IMI), and the non-specific monoamine oxidase inhibitor (MAOI) phenelzine were studied. Only phenelzine increased plasma corticosterone with the low dose, whereas phenelzine and DMI increased plasma corticosterone with the high doses when measured 30 min after drug administration. In a second experiment, it was observed that after 12 daily doses of the drugs (20 mg/kg), all drugs increased plasma corticosterone at 30 min after the last drug administration. When the circadian pattern of corticosterone was studied in the same experiment, starting on the day after the last drug administration, a significant interaction of drug by time of day was found. Drugs caused changes in the normal levels of plasma corticosterone at certain times and DMI, IMI and phenelzine reduced the number of rats showing the normal corticosterone peak at 1900 hours. No significant effect of drugs on corticosteroid-binding globulin (CBG) was found. In a third experiment, phenelzine and IMI were administered as before, but samples were taken at several times both on the day of the last drug administration and on the following day. The two drugs altered the normal circadian pattern of corticosterone in a somewhat different way, but both caused a reduction of the corticosterone peak at lights off on the day after the last drug administration. The normal relative thymus weight observed in all groups (exp. 2) suggests that the overall biological activity of corticosterone was probably not affected by antidepressants. The present results indicate that most antidepressants are able acutely to activate the PA axis after repeated administration in a similar way or even more-strongly than after the first administration, and that some of these drugs alter normal circadian pattern of corticosterone. No evidence for decreased resting PA activity was found in antidepressant-treated rats.

Anterior pituitary response to stress : time-related changes and adaptation

A wide array of physical and psychological stressors alter the secretion of anterior pituitary hormones. However, both the qualitative and the quantitative features of the stressors as well as its duration markedly influence the final endocrine response. In addition, among all anterior pituitary hormones, only ACTH and prolactin levels appear to reflect the intensity of the stress experienced by the animals. Although physical stressors show a somewhat specific neuroendocrine profile, the response of the pituitary-adrenal (PA) and sympathomedulloadrenal axes are common to almost all stressors. After an initial stimulatory effect of stress, an inhibition of all anterior pituitary hormones, except ACTH, can be found provided the stressor is intense enough. The mechanisms responsible for this biphasic response to stress are likely to be located at sites above the pituitary. When the animals are repeatedly exposed to the same stressor, some behavioural and physiological consequences of stress exposure are reduced, suggesting that the animals become adapted to the stimulus. This process has been also termed habituation. Among all the pituitary hormones, only ACTH and prolactin levels are reduced as a consequence of repeated exposure to the same (homotypic) stressor, although some negative results have been reported. However, it has been recently reported that subtle changes in the characteristics of the stressors or in their regularity can greatly influence adaptation, and these factors might explain failure to find adaptation of ACTH and prolactin in some works. Habituation of ACTH and prolactin, when observed, appears to be specific for the chronically applied stressor so that the potentiality of the PA axis and prolactin to respond to a novel (heterotypic) stressor can be preserved. In the case of the PA axis, an intact or potentiated response to a novel stressor is observed in spite of presumably negative feedback exerted by daily stress-induced glucocorticoid release and the high resting levels of glucocorticoids. This phenomenon has been termed as facilitation and can be unmasked alternating stress. Although with the exception of the PA axis, developmental aspects of anterior pituitary response to stress have been poorly studied, available data suggest that dramatic changes occur in some hormones during weaning, with some, but less profound, changes thereafter. Responsiveness to stressors appears to mature with age, but developmental patterns differ among the various anterior pituitary hormones.

The effect of environment on behavioural activity, ACTH, (β-endorphin and cortisol in pre-farrowing gilts

AbstractThis study examined the temporal relationships between behavioural activity and hormones associated with stress in gilts farrowing in two environments. Thirty-one Large White × Landrace gilts with indwelling jugular catheters were blood sampled daily (08.00 and 16.00 h) from 10 days before their expected parturition date (EPD). Five days before EPD they were moved to either a farrowing crate (C) with no bedding, or a pen (P) (2·5 m × 3·0 m) with straw provided and were blood sampled daily at 08.00, 12.00 and 16.00 h. Around 12 h before the onset of farrowing an extension was fitted to the catheter and blood samples were taken remotely at 30-min intervals. The posture of the gilts was recorded using 5-min scan samples over the 24 h pre-farrowing. The proportion of scans standing (an index of activity) was strongly affected by time (P &lt; 0·001) with peak levels at approximately 8 h pre-farrowing in both treatments, and by treatment (0·25 v. 0·33 (s.e.d. 0·03) for C and P gilts respectively; P &lt; 0·05). Plasma cortisol concentrations also increased before farrowing (P &lt; 0·001) reaching a peak at 12 to 6 h pre-farrowing. Crated gilts had higher cortisol concentrations than, penned gilts (overall mean 41·5 v. 30·7 (s.e.d. 3·8) [μg/l for C and P gilts respectively; P &lt; 0·05) at 24 to 12 (P &lt; 0·05), 12 to 6 (P &lt; 0·01) and 6 to 2 (P &lt; 0·05) h pre-farrowing. Plasma ACTH concentration showed a similar pattern to cortisol over the pre-parturient period, peaking at 12 h pre-farrowing in both treatments (time: P &lt; 0·001); crated gilts had significantly higher concentrations of ACTH at 6h pre-farrowing only (P &lt; 0·05). Plasma β-endorphin concentrations also showed a gradual rise (P &lt; 0·001) towards parturition; however no treatment differences were seen. These results suggest that the pituitary-adrenal (PA) axis is stimulated during pre-farrowing activity irrespective of farrowing environment. Crates, without bedding, further stimulate the PA axis over the pre-farrowing period perhaps by preventing nest-building. The rise in Q-endorphin may be involved in an endogenous defence against parturition pain.

Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose

The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.

Fawn-hooded rats show enhanced active behaviour in the forced swimming test, with no evidence for pituitary-adrenal axis hyperactivity

Fawn-hooded (FH) rats have been reported to have high basal corticosterone levels that can be normalized by antidepressant administration. In the present work, some behavioural and endocrine aspects were compared in FH and Sprague-Dawley (SD) rats. No interstrain differences in basal corticosterone levels or response to acute tail-cut stress were observed either in the morning or in the evening. Relative adrenal weight was lower in FH than SD, and relative thymus weight was, accordingly, higher in FH than SD rats. FH rats were hyperactive in the holeboard and showed behaviour similar to that of SD in the plus-maze. In contrast, FH rats showed greater levels of active behaviour (struggling) and lower levels of immobility than SD rats in the forced swimming test (FST). After desipramine (DMI) administration the differences between the two strains in the FST were more marked than in vehicle-treated animals. These results indicate that FH rats show no signs of pituitary-adrenal (PA) hyperactivity or depression-like behaviour, and therefore they are not an appropriate animal model of depression.

Sex-dimorphic psychomotor activation after perinatal exposure to (-)-delta 9-tetrahydrocannabinol. An ontogenic study in Wistar rats.

The ontogeny and the adult expression of motor behaviors were studied in male and female rats born from mothers exposed to delta 9-tetrahydrocannabinol (THC, 5 mg/kg) during gestation and lactation. Perinatal exposure to THC increased both rearing and locomotor activities in males and females at immature preweanling ages (P-15 and P-20). These effects disappeared after ceasing THC exposure (postweaning ages), but they were observed again in adult (P-70) females. The effects appeared as persistently high motor activity in familiar environments, disappearing the characteristic habituation profile in locomotor and exploratory behaviors. In novel environment condition tests, adult (P-70) THC-exposed females, but not males, exhibited lower locomotor activity in the socio-sexual approach test, and an increase in the emergence latency in the dark-light emergence test. Additionally, animals of both sexes exposed to THC showed a increase in the time spent grooming measured in novelty conditions. These findings suggest that perinatal exposure to THC affects both the development and the adult expression of motor behaviors and it resulted in a sex-dimorphic psychomotor activation very similar to that observed after perinatal exposure to other drugs of abuse. A possible role of THC-induced pituitary-adrenal (PA) axis activation was also evaluated by measuring plasma corticosterone levels in adult animals perinatally exposed: THC-exposed females exhibit a clear increase of this adrenal hormone, whereas THC-exposed males displayed lower levels of this hormone.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of acute and chronic ACTH administration on pituitary-adrenal response to acute immobilization stress. Relationship to changes in corticosteroid-binding globulin.

The effect of single and chronic ACTH administration on serum levels of the corticosteroid-binding globulin (CBG) and pituitary-adrenal (PA) responsiveness to acute immobilization (IMO) stress was studied in adult Sprague-Dawley rats. Single ACTH administration significantly reduced CBG levels but did not alter PA response to acute IMO. Chronic ACTH administration caused a greater fall in CBG than single ACTH administration and blunted PA response to IMO. The effect of chronic ACTH administration on CGB levels recovered 2 days after the last administration, but the ACTH response to IMO was normal only by day 7 after the last ACTH injection. The present data indicate that ACTH administration to rats reduced CBG levels and impaired PA response to acute stress, but impaired PA responsiveness cannot be solely attributed to changes in CBG.

Mechanisms of activation of the pituitary-adrenal axis by tissue injury in the rat

To characterize the mechanisms of the pituitary-adrenal (P-A) response to tissue injury, rats were injected intramuscularly (IM) with turpentine. This resulted in marked elevations in the plasma concentrations of ACTH and corticosterone within the first hour after injection, which were attenuated by either total deafferentation of the medial basal hypothalamus (MBH) or neonatal capsaicin pretreatment. The plasma concentrations of corticosterone remained elevated for 18 h in turpentine-injected rats, despite a return of ACTH toward control values (by 2–4 h). Bioactive concentrations of interleukin-6 (IL-6) in plasma rose markedly after turpentine, and its concentrations were significantly correlated with plasma corticosterone concentrations 4–8 h after turpentine. Pretreatment with IL-1 receptor antagonist (IL-1ra) attenuated the release of IL-6 and had a marginal effect on the corticosterone response 6 h after turpentine. These results suggest that the early and late phase of the P-A response to tissue injury are mediated by different mechanisms.

Negative feedback of corticosterone on the pituitary-adrenal axis is maintained after inhibition of serotonin synthesis with parachlorophenylalanine

The role of the serotonergic transmission on the negative feedback of corticosterone on the pituitary-adrenal (PA) axis was studied in adult male rats. Animals were given p-chlorophenylalaine (PCPA) and 24 h later were administered corticosterone, 2 h before being subjected to 20 min of noise stress. The main results were as follows: First, PCPA administration increased resting levels of both corticotropin (ACTH) and corticosterone but did not alter PA response to noise stress; second. ACTH response to stress was eliminated in rats given PCPA; third, corticosterone reduced ACTH levels in nonstressed rats only and this effect was maintained after PCPA administration. Taken together, the present results suggest a mediator role for serotonin in the noise-stress-induced PA hormone release but no role in the negative feedback of corticosterone on the PA axis.