Exogenous Adrenocorticotropic Hormone Research Articles

A case of feline primary hypoadrenocorticism

A 2-year-old entire female British Shorthair cat was referred to the University of Bristol for investigation of lethargy, weakness, constipation and hypothermia. Clinical examination revealed a profoundly weak, hypovolaemic and hypothermic cat. Serum biochemistry revealed hyponatraemia, hyperkalaemia and hyperphosphataemia and the urine was isosthenuric. Lack of response to exogenous adrenocorticotrophic hormone confirmed a diagnosis of hypoadrenocorticism. Treatment consisted initially of intravenous fluid therapy and subsequently a combination of fludrocortisone and prednisolone per os. At follow-up, 20 months after the initial diagnosis the cat remained stable and free of clinical signs.

Social and economic depression and depressive disorders in the elderly

1.1. Previous studies conducted in our laboratory demonstrated that rats given a choice between a 0.1% saccharin solution or 10% ethanol/0.1% saccharin solution and repeatedly exposed en an unpredictable basis to stressful stimuli, consumed increasing quantities of the ethanol solution following cessation of stressor presentation as compared to nonstressed control rats.2.2. Stressful stimuli potently activate the hypothalamic-pituitary-adrenocortical (HPA) axis, thus a systematic investigation of the HPA axis and its involvement in post-stress induced ethanol consummatory behavior was undertaken.3.3. Exposure to repetitive unpredictable stressful stimuli did not induce the free-choice consumption of ethanol in either hypophysectomized rats or chronic dexamethasone treated rats.4.4. Adrenalectomized rats exposed to chronic unpredictable stressful stimuli consumed increased quantities of ethanol following cessation of stressful stimuli in both a quantitative and qualitative manner which mirrored that of intact animals.5.5. Repeated intravenous administration of exogenous adrenocorticotropin (ACIH1–39) on an unpredictable basis also induced ethanol consuming behavior, following the discontinuation of its administration.6.6. These results suggest that elimination of the pituitary or pharmacological antagonism of stress-induced HPA activation will prevent post-stress induced ethanol consumnmatory behavior.7.7. Conversely, activation of a functional hypothalamic-pituitary system or repeated administration of exogenous ACTH1–39 will initiate ethanol consumption in rats.8.8. Thus, hormones secreted from the pituitary, namely ACIH, appear to play a crucial role In the post-stress Induced initiation of ethanol consuming behavior in rats.

Pharmacokinetics of exogenous corticotropin in normal dogs, hospitalized dogs with non adrenal illness and adrenopathic dogs.

Corticotropin (ACTH) pharmacokinetics was assessed in 10 normal dogs receiving exogenous ACTH (0.5 U/kg, i.v.). A two-compartment open model was most appropriate for description of exogenous ACTH pharmacokinetics. The apparent distribution and elimination rate constants (alpha and beta) were 7.4 +/- 2.7 x 10(-2) min(-1) and 5.5 +/- 3.8 x 10(-3) min(-1), respectively. Area under the concentration-time curve (AUC) was 2.91 +/- 0.78 x 10(4) pg x min/mL, mean residence time (MRT) was 45.0 +/- 12.2 min, the distribution half-life (t1/2alpha) was 9.4 min (harmonic mean), and the elimination half-life (t1/2beta) was 128 min (harmonic mean). The total body clearance of ACTH (ClB) was 1.83 +/- 0.46 x 10(4) mL x min/kg and volume of distribution (Vd(area)) was 30 +/- 15 L/kg. Corticotropin pharmacokinetics was also assessed in 12 client owned dogs, six dogs with non adrenal illness (NAI) and six dogs with hyperadrenocorticism (HAC), receiving exogenous ACTH (0.5 U/kg, i.v.). For these patients, data was best fitted to a one-compartment open model. In dogs with NAI, the AUC was 6.23 +/- 0.62 x 10(5) pg x min/mL, MRT was 38.7 +/- 12 min, the apparent elimination rate constant (k(el)) was 0.26 +/- 0.0017 min(-1) elimination half-life was 26.7 min, ClB was 0.84 +/- 0.1 x 10(4) mL/min/kg, and Vd(area) was 31.9 +/- 5.7 L/kg. In dogs with HAC, AUC was 4.74 +/- 0.23 x 10(5) pg x min/mL, MRT was 20.4 min, k(el) was 0.034 +/- 0.009 min(-1), half-life was 20.4 min, CIB was 1.06 +/- 6.0 x 10(4) mL/min/kg and Vd(area) was 29.7 +/- 6.7 L/kg. Dogs with pituitary-dependent hyperadrenocorticism showed more rapid elimination and clearance of exogenous corticotropin than dogs with NAI.

Relations between oral stereotypies, open-field behavior, and pituitary–adrenal system in growing dairy cattle

REDBO, I. Relations between oral stereotypies, open-field behaviour, and pituitary–adrenal system in growing dairy cattle. PHYSIOL BEHAV 64(3) 273–278, 1998.—The aim of this study was to investigate possible differences between calves with or without stereotypies concerning their behavioural reaction to an acute stress situation such as an open field and their behavioural and pituitary-adrenal responses to long-term tethering. Behavioural observations, open field tests, sampling for baseline adrenocorticotropic hormone (ACTH), and adrenocortical response tests after synthetic ACTH administration were made on 48 4- to 7-months-old dairy calves housed in tether stalls. Behavioural observations and blood sampling for baseline ACTH and cortisol determination after synthetic ACTH were repeated a year later in the same animals. Individual stereotypy levels showed a high correlation between calf values and heifer values ( p < 0.001). Baseline ACTH in the calves was related to individual stereotypy levels ( p < 0.05) in that the calves with higher stereotypy levels had lower ACTH values. The release of cortisol after injection of synthetic ACTH was considerably higher in the animals as heifers than when they were calves ( p < 0.001). There was a relation between adrenocortical response to ACTH and stereotypy level in the heifers, showing that the higher the stereotypy level, the lower the cortisol response ( p < 0.05). In the open field tests, the calves with the highest stereotypy levels moved around least but explored most. In conclusion, this study shows that growing dairy cattle with relatively high levels of oral stereotypies differ from individuals devoid of, or with low stereotypy levels, in behavioural response patterns to a short-term stressor such as an open field in adreno–cortical responses to exogenous ACTH and in baseline ACTH after 2 weeks of tethering.

Normal Short Synacthen Test in Patients with Secondary Adrenal Failure

The short synacthen test (SST), first introduced by Wood et al. 1 in 1965, is widely used to confirm the diagnosis of primary adrenal insufficiency. The optimum method for the diagnosis of secondary adrenal insufficiency remains controversial. The insulin tolerance test (ITT) is accepted by most endocrinologists as the gold standard 2 for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis, but is hazardous at times, with some morbidity and occasional mortality. The short synacthen test is gaining popularity, and by 1994, up to 50% of UK endocrinologists were using it to assess the HPA axis. 3 We describe two cases presenting with hyponatremia in whom hypoadrenalism was suspected, but with normal SST. The secondary adrenal insufficiency was later confirmed in these cases on clinical features, associated hormonal deficiencies, ancillary investigations and most important of all, the therapeutic response to replacement steroids. Case 1 A 63-year-old male presented with a history of six to seven episodes of fainting/loss of consciousness over the previous year-and-a-half. These episodes were never preceded by any palpitations or associated with seizure activity and/or incontinence of urine or feces. He also experienced occasional nausea with vomiting. He was labelled to have ischemic heart disease on the basis of ECG changes, but did not have angina and was taking diltiazem, moduretic (amiloride and hydrochlorothiazide), ranitidine and amitriptyline regularly. He appeared unwell upon admission, and was pale-looking, with a pulse of 90/min. His blood pressure was in the range of 120-140 mm Hg systolic and 70 mm Hg diastolic, but with a significant postural drop of 20 mm Hg. The rest of the examination was unremarkable. Routine investigations revealed serum sodium of 112 mmol/L, potassium of 3.3 mmol/L, and creatinine of 1.0 mg/dL. It was thought that electrolyte imbalance was due to diuretics and associated vomiting. He was rehydrated with normal saline and the

Neuromedin U enhances proliferation of ACTH-stimulated adrenocortical cells in the rat

Neuromedin U (NMU) is a brain-gut peptide involved in the regulation of the hypothalamic-pituitary-adrenal axis and adrenocortical cell proliferation. In this study, we investigated the effects of NMU8 (three subcutaneous injections of 6.0 nmol/100 g, 24, 16 and 8 h before autopsy) on the adrenal glands of rats treated for 2 or 4 days with a low (2 microg/100 g body weight/24 h) or a high (8 microg) dose of adrenocorticotropic hormone (ACTH). As revealed by RT-PCR, ACTH treatment did not prevent expression of NMUR1 in rat adrenal cortex. At day 4 of ACTH administration, the weight of adrenals was lower than at day 2. NMU8 administration prevented ACTH-induced increases of adrenal weight at day 2 of the experiment. ACTH plasma concentrations were increased in all ACTH-administered rats. NMU8 administration increased ACTH plasma concentration at day 2 of the lower ACTH dose-treated group while it reduced the ACTH plasma level at day 4 in the higher ACTH dose-administered rats. In all groups of ACTH-treated rats, NMU8 changed neither aldosterone nor corticosterone plasma concentrations. In the zona glomerulosa (ZG), NMU8 increased metaphase index at days 2 and 4 in the lower ACTH dose-treated group and had no statistically significant effect in rats treated with the higher ACTH dose. In the zona fasciculata (ZF), NMU8 administration increased metaphase index at day 2 in the lower ACTH dose-treated group but reduced metaphase index at day 4 in the higher dose ACTH-administered rats. NMU8 reduced the number of cells per unit area both in ZG and ZF at day 2 in the higher ACTH dose-treated rats. In the remaining groups NMU8 did not produce statistically significant changes in the number of cells per unit area. Thus, our findings demonstrate that exogenous NMU may stimulate proliferation primarily of the cortical ZG cells in rats administered with ACTH, although at high doses of exogenous corticotropin an opposite effect occurred.

Salivary vs. serum cortisol for the assessment of adrenal activity in swine

The efficacy of salivary cortisol analyses for assessment of the hypothalamic-pituitary-adrenal (HPA) response to stimulation is compared to serum cortisol measurement. Matched samples of serum and saliva were collected from pigs (n = 6) subjected to exogenous adrenocorticotrophic hormone (ACTH) stimulation (i.v. 200 IU) and snaring. Salivary cortisol responses to handling and transport (1 h) were measured in a further 10 pigs. Saliva samples were collected before and after handling and transport. There were significant correlations between serum and salivary cortisol values, following ACTH stimulation (r = 0.8813, P &lt; 0.025), and snaring (r = 0.7964, P &lt; 0.05). The overall ratio of saliva to serum cortisol was 9%. The saliva:serum cortisol ratio was concentration dependent. In pre-stimulation samples the ratio was 8.6% and at maximal concentrations was 13.3%. Handling and transport stress stimulated increases in salivary cortisol concentrations. Differences between pre- and post-transport concentrations were significant (P &lt; 0.0001). Variation in the concentration of cortisol-binding globulin (CBG) is an important factor for the interpretation of adrenal response. Salivary "free" cortisol may be a better indicator of stress than "total" cortisol measured in blood samples. Key words: Saliva, cortisol, pig, ACTH, transport, stress

Influence of exogenous and endogenousACTH on adrenal cortex activity in calves during the early postnatal period

A study was carried out on 66 black-and-white calves during the period from birth (day 0) to day 21 of life. Blood plasma adrenocorticotrophic hormone (ACTH) and cortisol concentrations were determined by radio-immunoassay and the influence of exogenous and endogenous ACTH on adrenocortical activity assessed. An ACTH-induced adrenal cortex response was observed as early as day 0, whereas a definite relationship between ACTH and cortisol concentrations emerged in the second week of life. It is concluded that the pituitary-adrenal axis is blocked during the first week of life and this effect seems to be related to high cortisol concentrations and an elevated reactivity threshold of the adrenal ACTH receptors.

Enhanced adrenal sensitivity to adrenocorticotrophic hormone (ACTH) is evidence of HPA axis hyperactivity in Alzheimer's disease.

Adrenal sensitivity was assessed in 16 non-depressed patients with NINCDS/ADRDA Alzheimer's disease (AD) and 18 control subjects by measuring cortisol response to low dose (0.05 microgram/kg i.v.) exogenous adrenocorticotrophic hormone (ACTH). Controlling for sex and medication, both peak cortisol level (peak-baseline) and area under cortisol response curve (AUC above baseline) were significantly greater in AD subjects. This shows that HPA axis hyperactivity, as demonstrated by enhanced adrenal sensitivity to ACTH, occurs in AD. Similar findings have been reported to occur in depression. Among AD subjects, AUC cortisol response correlated with current age (r = 0.70, P = 0.001) and age at onset of dementia (r = 0.73, P = 0.001) and an inverse correlation was seen between cortisol AUC and cognitive test (CAMCOG) score (r = -0.51, P = 0.044). Our findings suggest that HPA axis hyperactivity in AD is associated with advancing age and cognitive dysfunction. Such changes may be cause, or consequence, of neuronal loss.

Effects of a series of metalloporphyrins on adrenal, testicular and thyroid function in rats.

We have extended our earlier studies [Pharmacology 1986;34:9-16] on the effects of certain synthetic heme analogues and cobalt chloride (CoCl2) on endocrine functions mediated by the hypothalamic-pituitary axis to examine specifically the ability of Sn-protoporphyrin (SnPP) and Sn-mesoporphyrin (SnMP) to perturb adrenal, testicular and thyroid function since there is interest in the use of Sn(tin)-porphyrins in the treatment of hyperbilirubinemia of the newborn. SnPP and SnMP when administered to adult male rats did not alter serum corticosterone, testosterone, thyroxine or triiodothyronine levels when compared to control animals. In addition, administration of exogenous adrenocorticotrophic hormone produced an increase in serum corticosterone levels that was comparable in placebo-treated and SnPP- and SnMP-treated animals. These studies involved doses of both compounds substantially greater than those used clinically. The results clearly indicate that SnMP, presently the compound of choice for use in newborns, and SnPP do not in the doses studied impair adrenal, testicular and thyroid function in vivo.

Measurement of hippocampal glucocorticoid receptors in suicide

Increased adrenal cortex responsiveness to adrenocorticotropic hormone (ACTH) has been suggested to contribute to increased cortisol secretion in dexamethasone nonsuppression and melancholia. To further examine this hypothesis, the following variables were examined in 68 patients with unipolar depression (minor, n = 24; simple major, n = 25; melancholic, n = 19): basal or post-Synachten [ACTH(1–24), 250 μg IV] intact ACTH(1–39), β-endorphin/β-lipotropin, cortisol, and androstenedione concentrations, as well as the postdexamethasone (DST) (DST) plasma ACTH(1–39) and cortisol values. Melancholic subjects showed significantly higher baseline ACTH(1–39), β-endorphin/β-lipotropin, and androstenedione values compared with subjects with minor depression. No significant differences in post-Synacthen cortisol or androstenedione secretion between any of the groups or between [ACTH(1–39) or cortisol] DST nonsuppressors and suppressors were found. No significant relationships between DST and ACTH test results were observed. Abnormally increased post-DST cortisol values in melancholic subjects were highly preicted (68% of the variance) by post-DST intact ACTH levels. ACTH(1–39) values were significantly lower after Synacthen administration in melancholic subjects than in subjects with minor depression. These results are not consistent with the hypothesis that melancholia is characterized by an increased adrenocortical responsivity to exogenous ACTH compared with minor depression or that DST nonsuppression is due to adrenal hyperresponsiveness.

Patterns of interaction between the immune and endocrine systems in the manifestation of hereditary autoimmune disorders in NZB mice

Specific features of immune-endocrine interrelationships and of pituitary-adrenal system functioning are studied in NZB mice with hereditary autoimmune pathology. It is established that the development of disease is accompanied by a weakened response to stress, reduced blood corticosteroid level, and decreased adrenal reactivity to exogenous adrenocorticotropic hormone. Moreover, a loss of sensitivity to interleukin-2 is observed. These facts provide evidence of disturbed interaction between the immune and endocrine systems as well as of inhibition of pituitary-adrenal system activity as the autoimmune disease develops.

Reduction of mitotic rate in the wool follicle by cortisol

Cortisol reduces wool growth at the systemic and local level, but the minimum time for a response to take place has never been reported because the methods used to measure the changes require at least 4 days of wool growth. A technique using local intradermal colchicines to estimate mitotic rate in wool follicles has been used in the present study, and can measure changes in mitotic rate over periods as short as 2 h. Within the dose range 0 to 1000 8g, intradermal injections of cortisol into adrenalectomized sheep had no effect on mitotic rate in wool follicles within 6 h. Stimulation of endogenous release of cortisol using exogenous adrenocorticotrophic hormone in entire sheep, was similarly ineffective within 5 h. Further investigations using adrenalectomized sheep revealed that bolus injections of hydrocortisone also had no effect on mitotic rate within 5 h. A fourth experiment was conducted, in which 15 adrenalectomized sheep were infused with: a control infusate for 4 days, followed by this infusate containing cortisol at a rate equivalent to 0, 0.87 or 1-82 mg kg-1 day-1 for 4 days, followed by a further 4 days of control infusate. Five hours after the change from control to the cortisol infusate, there was no significant difference in mitotic rate between treatment groups when adjusted using mean mitotic rate in the pre-cortisol period as a covariate (P = 0.887). However, 29 h of infusion with cortisol was sufficient to bring about a significant reduction in mitotic rate (P = 0.034). During the following 3 days of cortisol infusion, mitotic rate was maintained at a significantly lower level in the treated groups (P = 0.018), with the greatest effect apparent in the group which received the highest dose of cortisol. At 53 h post-cortisol infusion, there was a significant recovery in both cortisol treated groups to mitotic rates significantly above those recorded in the pre-cortisol infusion period (P = 0.003), while mitotic rate remained unchanged in the group which received no cortisol. It is concluded that acute changes in plasma cortisol concentration are not likely to produce acute changes in wool growth, but a sustained elevation of plasma cortisol concentration will reduce the rate of wool growth by reducing mitotic rate in wool follicles.

Effects of pantoprazole on endocrine function in healthy male volunteers

In a randomized, double-blind, two-period crossover study, pantoprazole 40 mg or placebo were given orally to 12 male volunteers for 2 weeks each. There was a wash-out period of at least 1 week between the two treatment periods. The effects of pantoprazole or placebo on cortisol and testosterone (primary criteria), and tri-iodothyronine, thyroxine, thyroid-stimulating hormone, thyronine-binding protein, parathyroid hormone, insulin, glucagon, renin, aldosterone, follicle-stimulating hormone, luteotrophic hormone, prolactin and somatotrophic hormone were compared. In addition, intragastric 24-h pH, 24-h H(+)-activity, and volume of nocturnal gastric juice were determined by gastric aspiration technique. Pantoprazole did not influence plasma levels of testosterone, circadian cortisol concentrations or plasma cortisol levels after exogenous adrenocorticotropic hormone stimulation, as compared to placebo (P > 0.05, Koch's test). Furthermore, there were no clinically relevant changes with any of the other endocrine parameters. Pantoprazole significantly increased the median 24-h pH (group median 4.3 vs. 1.8; P < 0.001) and decreased 24-h H(+)-activity (4.0 vs. 22.6 mmol/L; P < 0.001). The volume of nocturnal gastric juice did not significantly differ between the two treatments. Pantoprazole was well tolerated and the frequency of adverse events was similar to placebo. No drug-related changes in laboratory values were observed. Pantoprazole did not influence endocrine function in healthy male volunteers during short-term treatment.

Effects of substance P on adrenal responses to acetylcholine in conscious calves.

The effect of intra-aortic infusions of substance P (SP; 10 or 20 pmol.min-1.kg-1) on adrenal responses to acetylcholine (4.5 nmol.min-1.kg-1 ia) have been investigated in functionally hypophysectomized calves given exogenous adrenocorticotropic hormone (0.7 pmol.min-1.kg-1). At the lower dose, SP had no effect on cortisol output. In contrast, SP inhibited the output of both catecholamines and enkephalins in response to acetylcholine, without affecting the output of corticotropin-releasing factor (CRF). Increasing the dose of SP to 20 pmol.min-1.kg-1 ia significantly reduced the outputs of both cortisol and CRF (P < 0.025 and 0.01 respectively). It is concluded that SP is capable of modulating both adrenal cortical and medullary responses to acetylcholine and that the latter are more sensitive to this influence than the former.

Effects of short- and long-term administration of phenobarbital on endogenous ACTH concentration and results of ACTH stimulation tests in dogs

Summary The effects of short-term phenobarbital administration were evaluated in 6 adult mixed-breed dogs that received phenobarbital (5 mg/kg of body weight, PO, q 12 h) for 8 consecutive weeks. Six additional dogs served as untreated controls. At 2-week intervals, endogenous adrenocorticotropic hormone (ACTH) concentration and cortisol concentration before and 2 hours after administration of porcine aqueous ACTH (2.2 IU/kg, M) were measured. By means of oneway ANOVA, we were not able to detect a significant (P ≥ 0.05) difference in endogenous ACTH concentration and cortisol concentration before and after exogenous ACTH administration within groups over time or between groups at any time. To evaluate effects of long-term phenobarbital administration, sera and plasma were collected from 5 epileptic dogs that had received phenobarbital for &gt; 2 years and had serum phenobarbital concentrations &gt; 20 μg/dl. Endogenous ACTH concentration and cortisol concentration, before and after administration of ACTH, were within established reference ranges for all 5 dogs. Together, these results suggest that phenobarbital administration alone does not affect endogenous ACTH concentration or response to exogenous ACTH administration in dogs, and that these may be valid screening tests for hyperadrenocorticism in most dogs receiving phenobarbital.

Increased cortisol response to exogenous adrenocorticotropic hormone in chronically stressed pigs: influence of housing conditions.

In a longitudinal experiment, the influence of tethered housing (a condition of chronic stress) on the reactivity of the adrenal cortex to exogenous ACTH was investigated in gilts. To that end, the plasma cortisol response to synthetic ACTH (1-24; 10 micrograms/kg of BW; i.v. bolus injection via a permanent catheter) was determined before and after prolonged tethered housing. Two systems for tethered housing were used, one more restrictive than the other with regard to possibilities for visual and tactile contacts with conspecifics and visual control over the environment. The ACTH treatment induced a marked, transient plasma cortisol response in all gilts studied, irrespective of their housing conditions. Long-term tethered housing increased the ACTH-induced cortisol response. Possible effects of the experimental procedure or age-related effects could be excluded, because in control gilts, which were housed loose during the entire experimental period, the cortisol response to ACTH remained unaltered. The chronic stress-induced increase in the ACTH-induced cortisol response was considerably more pronounced and persistent in gilts that were deprived of possibilities for social contacts with conspecifics and visual control over the environment than in gilts with such possibilities. These data indicate that in tethered gilts adaptational changes occur at the level of the adrenal cortex that affect the ACTH-induced adrenocortical response. In addition, not only physical restraint but also restriction of social contact and visual control play an important role in the development of these changes.

Adrenal responses to the peptide PACAP in conscious functionally hypophysectomized calves

Intra-aortic infusions of pituitary adenylate cyclase-activating peptide-(1-38) (PACAP) produced a dose-related fall in aortic blood pressure over the range of 4-40 pmol.min-1.kg-1 in the presence of exogenous adrenocorticotropic hormone-(1-24) (ACTH, 2 ng.min-1.kg-1 i.v.; P < 0.01). At the higher dose there was a significant fall in adrenal vascular resistance in the absence, but not in the presence, of ACTH. PACAP also produced a dose-related increase in right adrenal cortisol output over the same range, which was significantly greater in the absence of exogenous ACTH (P < 0.01). At the higher dose, PACAP produced small but significant increases in adrenal epinephrine and norepinephrine output (P < 0.01) both in the presence and the absence of ACTH. There was also a small rise in Met5-enkephalin output, and corticotrophin-releasing factor (CRF) was released in the presence, but not in the absence, of ACTH. It is concluded that PACAP is capable of exerting potent steroidogenic and vasodilator effects in the adrenal gland in the normal conscious calf and of releasing significant amounts of catecholamines, enkephalins, and CRF from the adrenal medulla. These findings identify PACAP as a candidate neuromodulator in the adrenal gland in this species.

Corticotropin secretagogues facilitate recovery of the hypothalamus-pituitary-adrenal axis suppressed by prolonged treatment with dexamethasone

Prolonged use of glucocorticoids (GCs) can cause prolonged suppression of the hypothalamus-pituitary-adrenal (HPA) axis. This study examined the possibility that corticotropin or its secretagogues such as vasopressin, corticotropin-releasing hormone (CRH), or insulin accelerate recovery of the HPA axis after prolonged treatment with dexamethasone (DEX). Suppression of the HPA axis was induced in rats by DEX at a dosage of 250 μ g 100 g body weight (BW)/d for 14 days, after which rats were administered saline, corticotropin (Cortrosyn 0.1 mg), ovine CRH (oCRH 6 μg), vasopressin (2 U), or insulin (2 U) each morning. Adrenal weight (AW), BW, plasma corticosterone, and corticotropin, as well as pituitary corticotropin content, decreased significantly after DEX treatment. The plasma corticotropin level was significantly elevated 7 days after discontinuation of DEX treatment (day 8) and remained so until day 11, whereas the pituitary corticotropin content had returned to normal on day 8. Plasma corticosterone was suppressed until day 8, but was not significantly different from normal on day 11. The AW was also decreased until day 4, but was not different from normal on day 8 or day 11. The BW of experimental rats remained subnormal during the study period. Treatment of DEX-suppressed rats with exogenous corticotropin induced adrenal hyperplasia, but suppressed the plasma corticotropin level and delayed the normalization of plasma corticosterone until day 11. The insulin-treated group differed in no respect from the saline-treated group. Treatment with oCRH or vasopressin for 8 days normalized plasma and pituitary corticotropin, as well as plasma corticosterone. Hypothalamic immunoreactive CRH (iCRH) did not differ among any treatment groups. In conclusion, prolonged DEX treatment in the rat causes marked suppression of each component of the HPA axis. Plasma corticotropin was elevated before the axis recovered. Vasopressin and oCRH significantly hasten recovery of the axis after DEX treatment. Corticotropin treatment induces adrenal hyperplasia, but delays recovery of the HPA axis after DEX treatment.

Stereotypies and cortisol secretion in heifers subjected to tethering

The aims of this study were to assess the effect of tethering on environmentally induced stereotypies and urine cortisol concentration in Swedish Red and White heifers, and to analyse a possible relationship between the performance of stereotypies and cortisol concentration. Three groups of heifers ( N=14) with oral stereotypies, mainly consisting of tongue-rolling, were studied during three consecutive autumns. Recordings of the duration and frequency of stereotypies were made from the second and third day after the heifers had been transferred from pasture and tethered indoors, and for 7 weeks thereafter. The four heifers from the previous year were also subjected to urine collection to determine total 24-h concentration of cortisol during Weeks 1–8 post-tethering. An adrenalcorticoid response test was conducted after 8 weeks of tethering. Exogenous adrenocorticotropic hormone (ACTH) was administered to heifers with, and without, stereotypies. All 14 heifers from the three cohorts showed the same pattern concerning time allocated to stereotypies during the 8 weeks post-tethering. From a zero-level in pasture, they increased the time spent performing stereotypies until Week 4, whereafter the stereotypy level decreased. The heifers all had similar patterns of cortisol concentrations during the observation period. The cortisol concentration was high during the first week after tethering (on average, 84.25 nmol l −1), but from the second week onwards the concentration was decreased. The ACTH test showed no difference in adrenal status between tethered heifers with, or without, stereotypies. There was no indication that individual variation in cortisol level was associated with the performance of stereotypies. This study shows that tethering after a grazing period leads to increased levels of stereotypies and high urine levels of cortisol.