Rise In Plasma Cortisol Concentration Research Articles

Effects of dermal dexamethasone application on ACTH and both basal and ACTH‐stimulated cortisol concentration in normal horses

There are no data available regarding the systemic (adverse) effects which might be induced by topical/dermal glucocorticoids (GCs) application in the horse. Besides their widespread use for the treatment of a variety of peripheral inflammatory disorders such as atopic dermatitis, eczemas or arthritis in the horse, their surreptitious application has become a concern in doping cases in competition/performance horses. Assessing both basal and ACTH-stimulated plasma cortisol as well as basal ACTH concentrations following application of dexamethsone-containing dermal ointment is necessary to determine influences on hypothalamus-pituitary-adrenal (HPA) axis. Ten clinically healthy adult standardbred horses (6 mares, 4 geldings) were rubbed twice daily each with 50 g dexamethasone-containing ointment on a defined skin area (30 x 50 cm) for 10 days. RIA and chemiluminescent enzyme immuno-metric assay were used to determine resting and ACTH-stimulated plasma cortisol and basal ACTH concentrations, respectively. HPA feedback sensitivity and adrenal function were measured by a standard ACTH stimulation test. Dermal dexamethasone suppressed significantly the resting plasma cortisol level (to 75-98%) below baseline (P < 0.001) within the first 2 days and decreased further until day 10. ACTH stimulation test showed a markedly reduced rise in plasma cortisol concentrations (P < 0.001 vs. baseline). Plasma ACTH level decreased also during topical dexamethasone application. The number of total lymphocytes and eosinophil granulocytes was reduced, whereas the number of neutrophils increased. No significant change of serum biochemical parameters was noted. Dermal dexamethasone application has the potential to cause an almost complete and transient HPA axis suppression and altered leukocyte distribution in normal horses. The effects on HPA axis function should be considered in relation to the inability of animals to resist stress situations. The data further implicate that percutaneously absorbed dexamethasone (GCs) may cause systemic effects relevant to 'doping'.

Pituitary, adrenal, immune and performance responses of mature Holstein × Friesian bulls housed on slatted floors at various space allowances

The effect of various space allowances on the pituitary, adrenal and immune responses and on performance was investigated in 72 mature Holstein × Friesian beef bulls. The animals (weighing 403 ± 3.5 kg) were blocked by weight and randomly assigned to two groups (familiar, F, and unfamiliar, UF) × three treatments (1.2, 2.7 and 4.2 m 2 per bull; n = 24 per space allowance), and housed for 83 days in 18 pens ( n = 4 per pen). Blood samples were collected on days −1, 0, 3, 14, 36 and 77 with respect to mixing and housing on day 0. The bulls were given exogenous adrenocorticotrophic hormone (ACTH) on day 3 and corticotrophin-releasing hormone (CRH) on days 14, 36 and 77. Basal plasma cortisol concentration was not affected ( P > 0.05) by mixing F and UF bulls. On day 3, basal cortisol was greater ( P < 0.05) in bulls housed at 1.2 than those at 2.7 and 4.2 m 2 space allowances while no effect was observed in ACTH-induced plasma cortisol concentration among treatments. Following CRH administration, there was no effect ( P > 0.05) of treatment and treatment × time on plasma ACTH concentration. On day 14, interferon-γ production was lower ( P < 0.05) in the bulls housed at 4.2 vs. 2.7 m 2 and was intermediate but not significantly different ( P > 0.05) for those housed at 1.2 m 2. Animals housed at either space allowances had significant ( P < 0.05) neutrophilia, lymphopenia, eosinopenia and decreased haemoglobin on day 3 compared with day 0. The liveweight gain from days 0 to 83 was lower ( P < 0.05) in bulls housed at 1.2 compared with those at 2.7 and 4.2 m 2. Housing bulls at 1.2 m 2 space allowance had a detrimental effect on their growth and was associated with an acute rise in plasma cortisol concentration (on day 3) compared with those having space allowances of 2.7 and 4.2 m 2/bull.

Evidence for Ototopical Glucocorticoid-Induced Decrease in Hypothalamic-Pituitary-Adrenal Axis Response and Liver Function

To clarify whether ototopical glucocorticoid treatment is associated with impaired hypothalamic-pituitary-adrenal axis (HPA) activity and altered hepatic metabolism, one commercially available dexamethasone-containing ointment was tested. At present, very little is known about the effects of ototopical glucocorticoid treatment on HPA and liver function. Ten beagle dogs received two daily therapeutic doses of dexamethasone (0.6 mg/ear) in the outer auditory canal for 21 d in a single-blind, placebo-controlled study. Resting cortisol concentrations were assessed before, during, and after treatment using an RIA system. Adrenal function and HPA feedback sensitivity were measured by a standard dose (250 microg) ACTH stimulation test. Serum biochemical and hematological parameters were measured, whether ototopical glucocorticoids affect hepatic function was studied, and blood cell counts were made. Ototopical dexamethasone treatment induced a marked suppression (to about 100%) of resting plasma cortisol concentrations below the placebo effect (P < 0.0001) within the first 11 d, and these remained reduced during the entire treatment period up to d 19. As well, an ACTH stimulation test found a markedly reduced rise in plasma cortisol concentrations (P = 0.0004). Concomitantly, significant increases in serum activities of alkaline phosphatase, gamma-glutamyl transferase, alanine transaminase, and aspartate transaminase were detected. Moreover, we found a significant reduction in differential leukocyte counts of eosinophils and lymphocytes, whereas neutrophils increased. Although cortisol levels and hematological parameters returned to baseline 7 d after treatment cessation, liver enzyme activities remained elevated. In conclusion, these findings suggest that after ototopical application, dexamethasone is sufficiently absorbed from the auditory canal to suppress HPA function as well as to alter metabolic and hemopoietic profiles. Thus, in long-term treatment of otitis externa or media, the systemic adverse suppression of HPA has to be considered in relation to stress exposure, whereas changes in serum enzyme activities may not be interpreted as hepathopathy.

Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling. At approximately 138 days of gestation, fetuses were killed, and adrenals were removed for cell culture and analyses of ACTH-R mRNA and protein. After 48 h, adrenocortical cells were stimulated with ACTH for 2 h, and the medium was collected for cortisol measurement. The same cells were incubated overnight with medium or medium containing ACTH or forskolin (FSK), followed by ACTH stimulation (as above) and cortisol and cellular ACTH-R mRNA analyses. HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH-R mRNA and protein levels by over 35%. HPD cells secreted significantly less cortisol than sham cells (3.2 +/- 1.2 vs. 47.3 +/- 11.1 ng.ml(-1).2 h(-1)) after the initial ACTH stimulation. Overnight incubation of HPD cells with ACTH or FSK restored cortisol responses to acute stimulation to levels seen in sham cells initially. ACTH-R mRNA levels in cells isolated from HPD fetuses were decreased by over 60%, whereas overnight incubation with ACTH or FSK increased levels by approximately twofold. Our findings indicate that the absence of the cortisol surge in HPD fetuses is a consequence, at least in part, of decreased ACTH-R expression and adrenal responsiveness.

Sleep, hormones and memory

Nocturnal sleep in humans is characterised by a unique pattern of endocrine activity. Secretory activity of the hypothalamo-pituitary-adrenal (HPA) system is maximally suppressed during the early part of sleep, which is dominated by slow wave sleep (SWS). Concurrently, release of growth hormone (GH) and prolactin reach a maximum. During the late part of sleep when rapid eye movement (REM) sleep is predominant, HPA secretory activity distinctly increases while the release of GH reaches a minimum and also prolactin concentrations decrease. Release of thyroid stimulating hormone (TSH) usually peaks in the evening and is suppressed during sleep. The regulatory effects of sleep and circadian rhythm on HPA secretory activity are synergistic so that sleep amplifies the effects of circadian oscillators. In contrasts, the effects of sleep and circadian rhythm on the release of TSH are antagonistic. The effects of sleep on the release of GH and prolactin appear to be rather independent from circadian rhythm. What are the functions of this sleep specific regulation of endocrine activity? Considering the essential role sleep plays for the consolidation of memories, in an ongoing series of studies we are testing whether the endocrine regulation during sleep serves to enhance the memory function of sleep. The first studies focussed on the role of pituitary-adrenal activity. SWS-rich early sleep has been demonstrated to benefit particularly the hippocampus dependent declarative memory system (storing facts and episodes). In contrast, REM sleep-rich late sleep appears to improve in particular procedural memory for skills, not depending on the hippocampus. Enhancing plasma glucocorticoid concentrations during SWS-rich early sleep completely blocked hippocampus dependent declarative memory consolidation, but did not affect hippocampus independent procedural memory. Also, procedural memory consolidation was not impaired when the rise in plasma cortisol concentration during late REM-sleep rich sleep was prevented by administration of metyrapone. The data underscore the importance of pituitary-adrenal inhibition during early SWS-rich sleep for efficient consolidation of declarative memories.

Differences in arginine vasotocin gene transcripts and cortisol secretion in trout with high or low endogenous melanin-concentrating hormone secretion.

Previous studies on trout suggest that melanin-concentrating hormone (MCH) acts at both hypothalamic and pituitary levels to restrain the release of adrenocorticotropic hormone and hence cortisol during stress. Using in situ hybridization, the present work examined whether high rates of MCH secretion were associated with changes in the synthesis of arginine vasotocin (AVT), one of the corticotropin secretogogues. It also examined whether high endogenous MCH secretion restrains cortisol secretion during intense as well as mild stress, and how exogenous MCH affects the rise in plasma cortisol following injection stress. Trout were reared in black- or white-coloured tanks for 1 year or more to achieve maximal differences in MCH secretion. Following a mild stress, cortisol secretion was greater in black-reared fish with low MCH secretion which is in line with previous findings but, following a more severe stress, plasma cortisol concentrations were similar in the two groups. Injection of MCH into black-adapted fish restrained the stress-induced rise in plasma cortisol concentration during the first hour but did not affect final cortisol values. In two separate experiments, AVT mRNA levels were significantly lower in the hypothalamus of black-reared fish. Possible explanations for this include a greater negative-feedback restraint by cortisol, which is likely to rise higher in black-adapted fish during the moderate, daily stresses of aquarium life; or the possibility that exposure to a white background may be psychologically stressful, stimulating AVT transcription. The possibility that MCH directly stimulates AVT transcription cannot be excluded but seems less likely. The results suggest that while MCH may restrain the release of hypothalamo-pituitary stress hormones under moderately stressful conditions, it does not restrain AVT synthesis.

Dysregulation of the hypothalamo-pituitary-adrenal axis is related to the clinical course of MS.

To investigate whether dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis is related to clinical characteristics in MS. The authors performed the combined dexamethasone-corticotropin-releasing hormone test (Dex-CRH test) in 60 MS patients and 29 healthy control subjects. In addition, the short adrenocorticotropic hormone (ACTH) test was performed in 39 consecutive patients. All patients had active disease and none were treated with glucocorticoids, immunosuppressants, or immunomodulators. The patients had an exaggerated rise in plasma cortisol concentrations in the Dex-CRH test (p < 0.05), indicating hyperactivity of the HPA system. The degree of hyperactivity was moderate in relapsing-remitting MS patients (n = 38; area under the time-course curve for cortisol [AUC-Cort] 226.2+/-38.9 arbitrary units [AU], mean +/- SEM), intermediate in secondary progressive MS patients (n = 16; AUC-Cort, 286.8+/-60.2 AU), and marked in primary progressive MS patients (n = 6; AUC-Cort, 670.6+/-148.6 AU). Differences were significant between the three patient groups (p < 0.005), and between control subjects (n = 29; AUC-Cort, 150.8+/-34.1 AU) and each patient group. Indicators of HPA axis activation correlated with neurologic disability (Kurtzke's Expanded Disability Status Scale), but not with the duration of the disease, number of previous relapses, previous corticosteroid treatments, or depressed mood (Hamilton Depression Scale). The ACTH test was normal in 31 of the 33 patients studied. HPA axis hyperactivity in MS is related to the clinical type of disease, with a suggestion of increasing HPA axis dysregulation with disease progression.

Stress enhanced reduction in peripheral blood lymphocyte numbers in dairy cows during endotoxin-induced mastitis

Two groups of Holstein dairy cows, which showed either high- (HC; n = 8) or low (LC; n = 10) plasma cortisol concentrations in response to a psychological stressor (novel–environment test) in their first lactation, were used 1 year later for studying the effects of psychological stress on various aspects of the host defence during endotoxin-induced mastitis. Social isolation was used as a stressor; endotoxin was used to activate the host defence. HC-cows appeared to be more stressed by the experimental procedure than LC-cows. One hour after having been isolated, rectal temperature increased (+ 0.59°C) in HC- but not in LC-cows. Handling, related to the intra-mammary administration of endotoxin, induced a higher increase in cortisol concentration in HC- than in LC-cows 1 h after injection. In addition, HC-cows vocalised significantly more frequently (595 ± 222) than LC-cows (81 ± 24) between 1.5 and 9.5 h after isolation. Between 3 and 5.5 h after endotoxin-treatment, cortisol concentrations increased profoundly in both LC- and HC-cows and peaked at 24.6 ± 3.8 and 22.8 ± 3.1 ng ml −1, respectively. The rise in plasma cortisol concentration was associated with a decrease in the number of circulating lymphocytes between 0 and 8 h post injection (PI). Between 8 and 10 h PI, the number of circulating lymphocytes in HC-cows further decreased (40%) to 1.58×10 6 cells ml −1 and remained so until 21 h PI. This was not the case with the LC-cows. The results show that a differing sensitivity of dairy cows to environmental stressors is associated with a significant difference in the number of circulating leukocytes following intra-mammary administration of endotoxin during a period of social isolation. The results further suggest that, apart from adrenocortical hormones, other factors related to general stress-responsiveness modulate the number of peripheral lymphocytes in dairy cows during endotoxin-induced mastitis. During environmental stress, these factors may enhance endotoxin-induced reduction in circulating lymphocyte numbers, particularly in cows that are sensitive to environmental stressors. As to the clinical relevance of these differences in stress responsiveness, no differences between LC- and HC-cows were found in disease incidence nor in duration of a disease episode during both the 1st and 2nd lactation. In the 2nd lactation, HC-cows tended to produce less milk than LC-cows.

Changes in plasma cortisol concentrations in bitches in response to different combinations of halothane and butorphanol, with or without ovariohysterectomy

Changes in plasma cortisol concentrations were assessed in bitches in response to nine treatments: control, anaesthesia, analgesia, analgesia followed by anaesthesia, anaesthesia followed by analgesia at intubation, anaesthesia followed by analgesia at extubation, anaesthesia plus surgery, analgesia followed by anaesthesia plus surgery, and anaesthesia plus surgery followed by analgesia. The anaesthetic was halothane, the analgesic was butorphanol (0·4 mg kg −1) and the surgery was ovariohysterectomy. Blood samples, for plasma cortisol assays, were taken regularly from before treatment for five hours and then again after 24 hours. A small transient rise in plasma cortisol concentration in the control group was attributed to mild distress associated with novel experiences. A more pronounced and protracted rise in cortisol concentration in the analgesia group was ascribed to a dysphoric state of bitches under the influence of the agonist-antagonist butorphanol. Halothane anaesthesia alone resulted in no change in plasma cortisol concentration. When butorphanol was given after anaesthesia was induced or while the animal was still under the influence of anaesthesia (immediately after tracheal extubation), there was no immediate rise in plasma cortisol concentration and low concentrations were maintained for up to 60 minutes after halothane withdrawal. A marked rise in plasma cortisol concentration, which was sustained above pretreatment values for at least five hours, occurred in all surgery groups. Giving intravenous butorphanol 30 minutes prior to surgery had no effect on the surgically-induced rise in plasma cortisol concentration and no effect on the postsurgical plasma cortisol concentration. In contrast, butorphanol given at extubation did reduce plasma cortisol concentrations during the postsurgical period. These observations did not support the hypothesis that preoperative use of butorphanol would reduce the cortisol response after surgery under halothane anaesthesia.

A primate model of anxiety

Pentylenetetrazol (PTZ; 30 mg/kg, im) produced an acute anxiogenic effect on the behaviour of a social colony of rhesus monkeys acclimatized to laboratory conditions. The animals exhibited hypervigilance, aggressiveness, tachypnea, piloerection and frequent change of posture and also had raised plasma cortisol levels. These effects of PTZ were antagonized by benzodiazepines (diazepam; 1 mg/kg, iv and alprazolam; 0.05 mg/kg, po). Non-benzodiazepine anxiolytic drug (buspirone; 10 mg/kg, po) blocked the behavioural effects but not the rise in plasma cortisol concentration. On the other hand, pretreatment with hypnosedative (promethazine; 5 mg/kg, im) or anticonvulsant (sodium valproate; 40 mg/kg, po) agents did not attenuate the effects of PTZ indicating the specificity of its anxiogenic response. The model, thus, seems suitable for evaluation of potential anxiolytic agents.

Possible causes of differences in glucose metabolism between Angora goats of two different phenotypes

AbstractPrevious results have shown that certain phenotypes of Angora goat differ in respect of glucose metabolism and it has been proposed that this is linked to the high incidence of abortions in this breed. The aim of this experiment was to investigate adrenal function, food digestion and nutrient partitioning as possible causes of differences in glucose metabolism between a phenotype which produces a relatively large amount of mohair of a large fibre diameter (high producers) and a phenotype which produces less mohair of a smaller fibre diameter (low producers). Two groups consisting of 15 3-year-old Angora bucks each and representing two different phenotypes were given a maintenance diet for the duration of the trial. Plasma glucose concentrations during a 4-day fast were lower (P &lt; 0·01) in high producers than in low producers and plasma glucose concentrations following insulin injection also fell to a greater extent in high producers than in low producers (P &lt; 0·05), indicating that high producers were less able to mantain plasma glucose concentrations during periods of increased demand than low producers. The decrease in glucose concentration following insulin injection was accompanied by a rise in plasma cortisol concentrations until 60 min after the insulin injection but there were no differences between phenotypes (P &gt; 0·05). Similarly, cortisol concentrations rose to a peak 60 min after ACTH injection and there were no differences between phenotypes (P &gt; 0·05). In both instances, the pattern of cortisol concentrations was consistent with normal adrenal function and there were no indications of adrenal insufficiency. Although differences in digestion were observed between phenotypes (P &lt; 0·01), these were small. There were no differences in nitrogen (N) intake or retention (P &gt; 0·05). High producers deposited substantially more (proportionately 0·56) N as fleece than low producers (P &lt; 0·01), and partitioned a greater proportion of N intake to fleece production (P &lt; 0·01). It was concluded that adrenal insufficiency was not implicated in the observed differences in glucose metabolism between phenotypes but differences in digestibility and nutrient partitioning may play a role.

Effects of local anaesthesia of 4 to 8 hours' duration on the acute cortisol response to scoop dehorning in calves.

To determine the effect of a long-acting local anaesthetic on the plasma cortisol response in calves dehorned using a scoop. A physiological study with controls. Seventy female calves, 3 to 4 months old, were divided into seven groups and dehorned by scoop with or without a long acting local anaesthetic (bupivacaine) which provides local anaesthesia for 3 to 4 h. In some treatment groups the local anaesthetic was given a second time, after 4 h, to give 8 h of anaesthesia. Blood samples were taken before and for 9 h after treatment and plasma cortisol concentrations were measured. Scoop dehorning caused a marked rise in plasma cortisol concentration, which returned to pre-dehorning values after 7 h. The cortisol concentrations of calves given bupivacaine were similar to those of control animals for 4 h after dehorning, but then a significant and protracted rise occurred, with concentrations returning to pretreatment values at about 9 h after dehorning. In calves given a second treatment of bupivacaine 4 h after dehorning, the plasma cortisol concentration remained similar to control values for 8 h after dehorning but then increased sharply. During its period of activity long-acting local anaesthetic prevented the rise usually seen after scoop dehorning in plasma cortisol concentrations; by inference it also alleviated the pain-induced distress caused by this procedure. However, when its effects had worn off the plasma cortisol values rose sharply indicating that animals still experienced pain-induced distress despite local anaesthetic being administered.

Effects of regional analgesia and/or a non-steroidal anti-inflammatory analgesic on the acute cortisol response to dehorning in calves

The effect of using a non-steroidal anti-inflammatory analgesic (ketoprofen) on the plasma cortisol response in calves dehorned with or without regional analgesia was determined. One hundred calves divided into 10 groups, four control and six dehorned, were used. Blood samples were taken before and after dehorning and plasma cortisol concentrations were measured. Dehorning caused a marked rise in plasma cortisol concentrations which returned to pretreatment levels after seven hours. The animals given ketoprofen before dehorning had a cortisol response similar to the dehorned animals for the first 1·3 hours after dehorning but then the plasma cortisol concentration returned to pretreatment levels. When animals were given a regional analgesic and ketoprofen the plasma cortisol concentrations were similar to control animals which had not been dehorned, with a small increase in plasma cortisol concentrations for the first hour after dehorning and then a rapid return to pretreatment values. This response was significantly lower than that seen in calves which received only regional analgesia. The results of this study suggest that a systemic analgesic should be combined with regional analgesia if the distress associated with dehorning is to be abolished.

Systemic immune changes following meal intake in humans.

Food intake represents a high intestinal antigen exposition requiring host defense. Besides local immune activation, this defense includes a coordinate systemic immune response, which may serve to support local immunity. This study examined influences of a standardized high-protein meal on peripheral blood mononuclear cell counts; on the in vitro mitogen-stimulated production of tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interferon-gamma; on the in vivo plasma levels of tumor necrosis factor-alpha and interleukin-6; and on plasma concentrations of cortisol and growth hormone. Ten healthy men (18-35 yr) participated in two experimental sessions in a balanced order. On one occasion, subjects fasted; on the other, they received a high-protein meal at 1230. Blood was sampled every 15 min. Whereas the numbers of neutrophils and platelets were increased for more than 2.5 h after meal intake (P < 0.01) lymphocyte counts decreased (P < 0.01). Meal intake also decreased the production of interferon-gamma but did not affect the production and plasma levels of the other cytokines. Changes in immune cell distribution and function were accompanied by a strong postprandial rise in plasma cortisol concentrations. Some of the systemic immune changes, like the emigration of lymphocytes, probably into extravascular abdominal tissues, may serve to support local immune defense.

Effects of morning rise in cortisol concentration on regulation of lipolysis in subcutaneous adipose tissue.

Cortisol has a well-defined circadian rhythm. The aim of the study was to examine the effect of the morning rise in cortisol concentration on lipolysis in adipose tissue. Ten healthy subjects were studied on two occasions, and six of these were studied on three occasions. During the first two occasions, either a control or cortisol suppression study was performed by using metyrapone, and on the third occasion exogenous cortisol replacement was given in addition to metyrapone. Lipolysis in the subcutaneous adipose tissue of the anterior abdominal wall was studied by measurement of arteriovenous differences. Reduction in the early morning rise in cortisol led to significantly decreased venoarterialized differences for nonesterified fatty acids (P < 0.05) and glycerol (P < 0.01), attributable in part to decreased hormone-sensitive lipase (EC 3.1.1.3) action (P < 0.05) in adipose tissue. At the same time the arterialized plasma triacylglycerol concentration increased (P < 0.005) with a significant reduction in the adipose lipoprotein lipase (EC 3.1.1.34) rate of action (P < 0.05). In the replacement study, values were identical to those of the control study, showing that metyrapone had no nonspecific effects on lipolysis. We conclude that the morning rise in plasma cortisol concentration plays an important role in the regulation of lipolysis in adipose tissue in normal healthy adults.

Use of long-acting neuroleptics to reduce the stress response to management practices in red deer

Three groups of six adult red deer hinds were used to determine whether long-acting neuroleptic (LAN) tranquillisers were able to modify the behavioural and physiological responses of the deer to a range of routine management stressors: such drugs may eventually prove useful in capture procedures for wild animals. While the stressors increased moving activity and decreased inactive lying and inter-animal distances, these changes were reduced in LAN-treated animals. Blood samples, collected remotely using automatic equipment, showed that following application of the stressors there was a distinct rise in plasma cortisol concentrations which returned to pre-treatment levels more rapidly in LAN-treated animals. However, there was no effect of LAN treatment on plasma concentrations of creatine phosphokinase (CPK), aspartate aminotransferase (AST), total protein or testosterone. Overall, LAN-treated animals had higher concentrations of plasma thyroxine. Heart rate increased in response to the stressors and while the LAN-treated deer showed a greater increase, as with plasma cortisol concentrations, heart rate returned to baseline more rapidly in these animals. We conclude that LANs may have a role to play in wild deer capture and habituation to farming conditions through a reduction in fear and anxiety, but that further work is required to determine an optimal strategy.

Is the growth hormone concentration regulated by the morning rise in the plasma cortisol concentration?

Exogenous steroids affect plasma growth hormone (GH) concentrations and hypothalamic somatostatin levels either directly, by stimulating the anterior pituitary gland, or indirectly by partially inhibiting the response of the pituitary gland to stimuli. The effect of the circadian rhythm of cortisol on plasma GH concentrations is unknown. In normal subjects, highest plasma GH concentrations are recorded within the first two hours of onset of sleep. During the early morning the plasma GH concentration decreases and the plasma cortisol concentration increases. We investigated the effect of the early morning rise in plasma cortisol concentration on plasma GH concentrations. We studied 12 healthy volunteers on two occasions. On one occasion the early morning rise in plasma cortisol concentrations was reduced by administering metyrapone (750 mg, 4 hourly from 03.00), while on the other occasion no intervention was made. Plasma GH and cortisol concentrations were measured every 30 and 60 minutes respectively from 22.00 until 14.00. Metyrapone caused a significant reduction in the rise of plasma cortisol concentration, but the GH concentration was identical on both occasions. We conclude that the morning rise in cortisol concentration has no acute regulatory effect on the plasma GH concentration.

Reduced Swimming Performance of Striped Bass after Confinement Stress

Length of confinement in a dip net affected subsequent performance of 2–3-year-old striped bass Morone saxatilis in a swimming challenge. Fish that were not confined or were confined for only 5 min could consistently swim for 10 min at 100 cm/s, whereas fish confined for longer than 15 min often could not. Average swimming time was significantly less for striped bass confined for 15 min or longer than for unconfined controls. Plasma cortisol, glucose, and lactate concentrations were always higher in fish after a swimming challenge than in resting fish sampled from the holding tank, although length of net confinement before swimming had little effect on postchallenge plasma variables. Time of postchallenge blood sampling, however, had a significant effect on all three plasma variables: glucose and cortisol concentrations were higher in striped bass immediately after they were removed from the swimming chamber, whereas lactate concentration was higher after 45 min of recovery. Resting and stress levels of the plasma variables resembled those measured in other fishes, except for the extremely large and rapid rise in plasma cortisol concentration from less than 50 ng/mL in resting fish to over 500 ng/mL in fish that had swum for 10 min.

The use of low doses of ACTH in the investigation of adrenal function in man

We have investigated the adrenal response, in eight healthy adult men, to low doses of ACTH(1-24) in order to define a dose which will elicit a response similar to that obtained with the short Synacthen test. The studies were performed at 14.00 h and blood samples were withdrawn at 5-min intervals after an i.v. bolus injection of ACTH(1-24). The sampling interval was crucial in determining the timing of the peak response. Using sampling times of 0, 10, 15, 20, 25 and 30 min ensured detection of 47 out of 48 peaks. A dose-dependent rise in plasma cortisol concentration was observed with bolus injections of ACTH(1-24) between 30 and 250 ng/1.73 m2 body surface area. Increasing the dose to 500 ng/1.73m2 (500 times less than that used in the short Synacthen test) elicited an increment of plasma cortisol concentration of 200 nmol/l or greater in all subjects. Pretreatment with dexamethasone (1 mg) did not alter the timing of the peak cortisol concentration but blunted the increase (pretreatment: median, 159 nmol/l; range 83-239; on dexamethasone; median 62 nmol/l; range 21-207; P = 0.04). These data suggest that a dose of ACTH(1-24) of 500 ng/1.73 m2 satisfies the criteria of the short Synacthen test and may provide a useful method of investigating adrenal function.

Endocrine responses to intra-aortic infusions of acetylcholine in conscious calves.

1. Adrenal responses to intra-aortic infusions of acetylcholine (4.5 nmol min-1 kg-1 for 10 min) have been investigated in conscious, functionally hypophysectomized, 3- to 6-week-old calves, in the presence and absence of exogenous ACTH (2 ng min-1 kg-1, I.V.). 2. Acetylcholine produced a substantial fall in adrenal vascular resistance, which was significantly reduced in the presence of exogenous ACTH, while producing minimal changes in aortic blood pressure and heart rate. 3. There was also a significant rise in right adrenal cortisol output which was sufficient to produce a measurable rise in plasma cortisol concentration. The effect could be accounted for by the increase in adrenal ACTH presentation. It was abolished by pre-treatment with atropine (0.2 mg kg-1). A small but significant rise in aldosterone output during acetylcholine infusions was also abolished in the presence of ACTH. 4. Both adrenaline and noradrenaline were released during intra-aortic acetylcholine infusions and these responses were substantially reduced, but not abolished, by pre-treatment with atropine. 5. Acetylcholine also stimulated the release of corticotrophin-releasing factor (CRF) and [Met5]enkephalins from the gland. The output of CRF was enhanced and that of free [Met5]enkephalin was significantly reduced in the presence of exogenous ACTH. All these responses were largely, but not completely, suppressed by atropine. 6. Acetylcholine also promoted the release of the pancreatic hormones glucagon, insulin and pancreatic polypeptide (PP). The amounts of pancreatic glucagon and insulin that were released were highly dependent on the concentration of glucose in the circulating plasma and all these responses were abolished by atropine. 7. It is concluded that acetylcholine is capable of stimulating the release of a wide variety of agonists from the adrenal gland when infused intra-aortically at a dose of 4.5 nmol min-1 kg-1. The increase in cortisol output appears to be secondary to an increase in blood flow whereas the adrenal medullary responses are not, and appear to be due largely, but not entirely, to activation of muscarinic receptors.