Exogenous Adrenocorticotropic Hormone Research Articles

Adrenal cortical and medullary responses to acetylcholine and vasoactive intestinal peptide in conscious calves.

1. Adrenal responses to intra-aortic infusions of acetylcholine and vasoactive intestinal peptide (VIP) have been investigated in functionally hypophysectomized calves given exogenous adrenocorticotrophic hormone (ACTH, 2 ng min-1 kg-1 I.V.). 2. Infusions of VIP at a dose of 0.13 micrograms min-1 kg-1 caused a small, but significant increase in adrenaline and noradrenaline output which was, however, far below the level recorded previously in response to acetylcholine (0.7 micrograms min-1 kg-1). In contrast, these doses of the two agonists produced closely similar rises in adrenal cortisol output. 3. The steroidogenic effects of acetylcholine and VIP were found to be strictly additive and no evidence of potentiation was obtained in relation to either cortical or medullary responses or in the case of any of the cardiovascular responses which were monitored. 4. Intra-aortic infusions of VIP, at a dose which produced a substantial increase in adrenal steroidogenesis (0.065 micrograms min-1 kg-1), had no effect on the output of catecholamines, enkephalin-like immunoreactivity or corticotrophin-releasing factor, either in the presence or absence of acetylcholine. 5. It is concluded that VIP is unlikely to modulate adrenal medullary responses to muscarinic stimulation in this species as it has been claimed to do in the rat and does not potentiate adrenal steroidogenesis in response to acetylcholine as it does to ACTH.

Modified responses of circulating cortisol, thyroid hormones, and glucose to exogenous corticotropin and thyrotropin-releasing hormone in food-deprived sheep

In a previous experiment, food deprivation was found to suppress the increase of plasma cortisol and thyroid hormones in stressed animals. Because both the hypothalamo-adrenocortical and the thyroid axes are stimulated during stress, we investigated in this study whether a similar pattern of changes occurs in food-deprived sheep following corticotropin (ACTH) or thyrotropin-releasing hormone (TRH) administration. Each hormone was given as a bolus injection on the fifth day of food deprivation. Blood was sampled by venipuncture five times: 0.5 h before and 1, 3, 5, and 9 h after injection of the hormone. The peak of plasma cortisol in food-deprived sheep following ACTH administration exceeded fourfold the corresponding peak in fed animals. This suggests that food deprivation may enhance the sensitivity of the adrenocortical gland to ACTH and/or reduced binding sites for cortisol in target tissues. In fed animals, TRH was without effect on plasma cortisol level, whereas in food-deprived sheep cortisol transiently increased 2.5-fold, suggesting greater permeability of the blood-brain barrier for TRH. In food-deprived animals, plasma T 3 was decreased to 22.6% of basal level, and elevated plasma cortisol after ACTH injection was not able to decrease it further. On the other hand, in fed sheep increased plasma cortisol did decrease plasma T 3 as much as 4.2-fold. Circulating T 4 was not affected by ACTH treatment. The Δ increase of plasma T 3 and T 4 following TRH administration was comparable in fed and fasted animals. In contrast, the maximal plasma levels of both hormones were always lower in fasted animals by about 25% due to lowered basal level, suggesting that food deprivation preserves the sensitivity of the hypothalamo-thyroid axis. Administration of ACTH to fed animals increased plasma glucose by 62% above basal level. Food deprivation lowered plasma glucose. A high level of endogenous cortisol following ACTH injection raised plasma glucose only by 19.5%. The results obtained suggest the lesser effectiveness of cortisol in food-deprived animals.

Pituitary and adrenal hormone responsiveness to synachten in melancholic subjects versus subjects with minor depression

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.

Physical contact with the boar is required for maximum stimulation of puberty in the gilt because it allows transfer of boar pheromones and not because it induces cortisol release

Two studies were conducted in which we examined the endocrine and pubertal response of gilts to boar exposure and adrenocorticotropic hormone (ACTH) injections in order to establish whether physical contact with the boar is essential for maximal stimulation of puberty because it initiates endocrine changes via a release of cortisol, or because it permits the physical transfer of primer pheromones present in boar saliva. Three experiments were performed in Study 1. Experiment 1 established that the dose of exogenous ACTH required to mimic the endogenous release of cortisol seen in gilts in response to full boar contact in previous studies was 10 IU given intramuscularly. In Experiment 2, the treatments were imposed for 31 days from a mean gilt age of 168.0 ± 1.35 days and consisted of: (1) control (isolated from boars); (2) isolated and injected with 10 IU ACTH each day; (3) daily fenceline contact with a mature boar; (4) daily fenceline boar contact plus ACTH; (5) full physical contact with a mature boar each day. Injection of ACTH caused a rapid acute elevation in plasma cortisol in all treatments and on all days when samples were collected (days 1, 3, and 5). Among gilts not given ACTH, plasma cortisol secretion was elevated only in the fenceline boar contact treatment. Overall, a significantly higher proportion of gilts reached puberty in response to full boar contact than in response to either the control, fenceline, fenceline plus ACTH or ACTH alone treatments (overall, 12/15 vs. 14/46, P < 0.01). In Experiment 3, treatments 1, 3 and 5 in Experiment 2 were repeated, along with the two additional treatments of daily contact with a mature boar restricted in a cage, and daily contact with the caged boar plus injection of 10 IU ACTH. Treatments commenced at a mean gilt age of 170.1 ± 0.61 days and continued for 28 days. The pubertal response to the two caged boar treatments (8/16 gilts) was intermediate between the control (1/7) and full contact treatments (6/7). Injection of ACTH had no effect on the efficacy of the control, fenceline or caged boar treatments. In Study 2 the treatments were imposed for 130 days from a mean gilt age of 159.8 ± 1.8 days and consisted of: (1) control (isolated from boars); (2) daily full physical contact with a mature boar with the gilts wearing a snout mask; (3) daily unrestricted full physical contact with a mature boar. The mean interval from start of treatment until puberty was significantly longer for the control gilts (30.3 ± 1.28 days) than for the masked gilts (17.4 ± 1.13 days, P < 0.05) or the full contact gilts (9.1 ± 1.11 days, P < 0.001). The mean interval for the full contact gilts was shorter ( P < 0.001) than for the masked gilts. The results of these experiments do not provide any evidence that an elevation in plasma cortisol is causally involved in mediating the stimulation of precocious puberty by boar contact. In contrast, the present results indicate that physical contact with the boar is essential for a maximal pubertal response because the priming pheromones from the boar need to be directly transferred to the snout of the recipient gilts.

The role of corticotrophin releasing factor in relation to the neural control of adrenal function in conscious calves.

1. Adrenal responses to intra-aortic infusions of pure synthetic ovine corticotrophin releasing factor (CRF), and to electrical stimulation of the preganglionic sympathetic innervation, have been investigated in functionally hypophysectomized conscious calves, in the presence and absence of a specific CRF antagonist. 2. CRF exerted a substantial steroidogenic effect on the adrenal gland of functionally hypophysectomized calves when infused intra-aortically at a dose (1.3 ng min-1 kg-1) below that which caused any fall in the arterial blood pressure. This response was significantly reduced, but not abolished by a concomitant infusion of CRF-antagonist into the aorta. 3. The steroidogenic effect of CRF was significantly reduced in the presence of exogenous adrenocorticotrophic hormone (ACTH) (2 ng min-1 kg-1, I.V.) and the surviving response was completely abolished by CRF-antagonist. 4. Stimulation of the peripheral end of the splanchnic nerve at 4 Hz in functionally hypophysectomized calves given exogenous ACTH produced a rise in mean adrenal output of the same order of magnitude as did exogenous CRF under the same conditions. The response to splanchnic nerve stimulation was apparently unaffected by CRF-antagonist although release of endogenous CRF from the gland was significantly increased thereby. 5. These results indicate that release of CRF from the adrenal gland during splanchnic nerve stimulation in the calf does not contribute significantly to the steroidogenic response thereto.

Muscarinic adrenal responses to 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 hypophysectomized conscious calves given exogenous adrenocorticotrophic hormone (ACTH) (2 ng min-1 kg-1 I.V.) in the presence and absence of hexamethonium. 2. Acetylcholine produced a significant increase in adrenal cortisol output and plasma cortisol concentration. In the absence of nicotinic blockade with hexamethonium this was apparently accounted for by an increase in adrenal ACTH presentation secondary to increased adrenal blood flow. However, administration of hexamethonium revealed a direct steroidogenic action of acetylcholine in the presence of exogenous ACTH. 3. Adrenal medullary responses to acetylcholine, including the release of catecholamines, enkephalins and corticotrophin-releasing factor (CRF), were not significantly reduced by nicotinic blockade. 4. It is concluded that both adrenal medullary and cortical responses to intraaortic infusions of acetylcholine at a low dose are mediated mainly by muscarinic receptors, as it has previously been shown that they are substantially reduced in the presence of atropine.

The welfare of pigs in two farrowing/lactation environments: cortisol responses of sows

Plasma free cortisol concentrations were measured in 24 primiparous sows housed from Day 104 after mating up to Day 2 after parturition. Concentrations were measured in 22 of these sows, from Days 2–29 of lactation, housed in either commercial farrowing crates (Crate treatment) or farrowing pens with straw added (Pen treatment). The mortality and growth data of litters from the time of birth to weaning were also recorded. The mean plasma free cortisol concentration was higher in sows housed in the Crate treatment, compared with sows housed in the Pen treatment, on the first day of treatment (8.2 and 5.8 nmol l −1, respectively, P < 0.05) and on Day 28 of lactation (5.6 and 4.0 nmol l −1, respectively, P < 0.05). The data suggest that housing treatment around parturition and during lactation may have only limited effects on the welfare of sows, providing that lactation is no longer than 28 days. On Days 21 and 24, there were no effects of treatment on free cortisol concentrations and no response to the exogenous adrenocorticotrophic hormone (ACTH), respectively. However, on Day 28, there were mean increases in the concentrations of free cortisol of approximately 150% and approximately 60%, respectively; these may have been the result of unavoidable attention of the piglets to the sows.

Lack of coupling between adrenal cortical metabolic activity and blood flow in anesthetized dogs.

To determine whether adrenal O2 consumption and cortical blood flow (CBF) increase during stimulation of cortical secretory activity, exogenous adrenocorticotrophic hormone (ACTH) was infused at 0, 2, and 10 ng.kg-1.min-1 (groups 1, 2, and 3, respectively) into dexamethasone-pretreated, pentobarbital-fentanyl-anesthetized, ventilated dogs. ACTH levels of approximately 20, 100, and 500 pg/ml were obtained in groups 1, 2, and 3, respectively. Cortisol secretion increased after 20 min in groups 2 and 3 (from 0.016 +/- 0.004 to 2.25 +/- 1.36 and from 0.02 +/- 0.01 to 5.32 +/- 1.23 microgram.min-1.g cortex-1, respectively) while adenosine 3',5'-cyclic monophosphate (cAMP) secretion increased after 20 min only in group 3 (from 5.7 +/- 2.8 to 61.3 +/- 18.6 micrograms.min-1.g cortex-1). Whole adrenal gland O2 consumption increased after 20 min in group 3 animals (from 0.89 +/- 0.16 to 1.77 +/- 0.27 ml O2.min-1.100 g tissue-1) but not in the other two groups. CBF measured with radiolabeled microspheres was unaffected by ACTH infusion while O2 extraction increased from a baseline of 5.9 +/- 1.4 to 13.0 +/- 2.4% after 30 min in group 3. These data demonstrate that in anesthetized dogs increases in adrenal cortical secretory activity are associated with increases in O2 consumption, and this increase in O2 consumption is met by increasing O2 extraction, not by increasing cortical blood flow.

The effect of chronic exercise on the pituitary-adrenocortical response in conscious rats.

1. This study was designed to investigate the effect of chronic exercise on exercise-induced changes in plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosterone in rats. Corticotrophin releasing factor (CRF) and ACTH were injected I.V. in order to assess the responsiveness of the pituitary and adrenal glands after chronic exercise. 2. The concentrations of ACTH and corticosterone in the plasma increased significantly after acute exercise in both the control and the exercised groups but both responses were significantly smaller in the exercised group. 3. The ACTH response to I.V. CRF was also significantly smaller in the exercised rats. However, both groups of animals showed similar increases in plasma corticosterone levels after the administration of exogenous ACTH. 4. The ACTH response to CRF attenuated by repeated administration of CRF. 5. These results suggest that attenuated ACTH and corticosterone responses to acute exercise after chronic exercise result from reduced responsiveness of the pituitary gland to CRF.

Acquired Partial Corticosterone Methyl Oxidase Type II Defect in Diabetes Mellitus: Case of Hyperreninemic Hypoaldosteronism

The aim of this study was to investigate the pathogenesis of hypoaldosteronism in diabetes. Endogenous elevation of plasma renin activity and exogenous corticotropin were used to study steroidogenesis. Observations were made over 12 yr on the evolution and treatment of hyperkalemia in a diabetic subject. In 1977, potassium, baseline cortisol, aldosterone, and renin activity were normal; renin activity increased normally with posture; and cortisol responded normally to ACTH infusion. Nine yr later, persistent hyperkalemia was documented. Upright renin activity was elevated to 5.26 ng.L-1.s-1, with concomitant elevation of 18-hydroxycorticosterone (18-OHB) and a low-normal aldosterone level. One hour after administration of 0.25 mg i.m. cosyntropin, cortisol increased normally, aldosterone increased from 220 to 360 pM, and 18-OHB increased from 3700 to 4800 pM. During treatment with fludrocortisone, fludrocortisone with furosemide, and furosemide alone, improvement of hyperkalemia was noted. Endogenous hyperreninemia and basal elevations of 18-OHB, accompanied by limited aldosterone responsiveness to renin and ACTH, suggest the presence of a partial corticosterone methyl oxidase type II defect. Evolution of hyperkalemia between 1977 and 1986 suggests this defect was acquired.

Effects of mevinolin, an inhibitor of cholesterol synthesis, on the morphology and function of differentiating and differentiated rat adrenocortical cells in primary culture

Mevinolin, an inhibitor of cholesterol synthesis, was used to study the effect of endogenous cholesterol synthesis on the morphology and function of differentiating and differentiated fetal rat adrenocortical cells grown in primary culture. Upon adrenocorticotrophic hormone (ACTH) stimulation under conditions in which endogenous cholesterol synthesis was inhibited but exogenous (lipoprotein) cholesterol was available, the cells differentiated normally from glomerulosa-like to fasciculata-like cells; the steroid hormone secretion was maximally induced. Under conditions in which cholesterol synthesis was maximally inhibited by mevinolin and the cells had no access to exogenous cholesterol, the cells did not differentiate into fasciculata-like cells; the ACTH-induced steroid response was highly suppressed under these conditions. The addition of either human low-density lipoprotein (LDL) or high-density lipoprotein (HDL3) to the culture medium restored the ACTH-induced differentiation and steroid secretion. Thus, in the absence of exogenous cholesterol, endogenous cholesterol synthesis was a prerequisite for differentiation. In cultures grown in the presence of exogenous cholesterol and ACTH with mevinolin-inhibited cholesterol synthesis and high steroid output, an increase in cytoplasmic lipids was evident, suggesting upregulation of LDL and HDL receptors. The results also demonstrated that induction of phenotypic differentiation from glomerulosa-like into fasciculata-like cells can proceed in the presence of a cholesterol synthesis inhibitor like mevinolin; this differentiation in the absence of endogenous cholesterol synthesis is accompanied by the appearance of cytoplasmic cholesterol ester droplets, typical of fasciculata cells.

Plasma cortisol response to ketoconazole administration in dogs with hyperadrenocorticism

Summary The effect of orally administered ketoconazole on plasma cortisol concentration in dogs with hyperadrenocorticism was evaluated. Every 30 minutes from 0800 hours through 1600 hours and again at 1800 hours, 2000 hours, and 0800 hours the following morning, 15 clinically normal dogs and 49 dogs with hyperadrenocorticism had plasma samples obtained and analyzed for cortisol concentration. The mean (± sd) plasma cortisol concentration for the initial 8-hour testing period was highest in 18 dogs with adrenocortical tumor (5.3 ±1.6 µg/dl), lowest in 15 control dogs (1.3 ± 0.5 µg/dl), and intermediate in 31 dogs with pituitary-dependent hyperadrenocorticism (pdh; 3.4 ± 1.2 µg/dl). Results in each of the 2 groups of dogs with hyperadrenocorticism were significantly (P &lt; 0.05) different from results in control dogs, but not from each other. The same cortisol secretory experiment was performed, using 8 dogs with hyperadrenocorticism (5 with pdh; 3 with adrenocortical tumor) before and after administration at 0800 hours of 15 mg of ketoconazole/kg of body weight. Significant (P &lt; 0.05) decrease in the 8-hour mean plasma cortisol concentration (0.9 ± 0.2 µg/dl) was observed, with return to baseline plasma cortisol concentration 24 hours later. Twenty dogs with hyperadrenocorticism (11 with pdh, 9 with adrenocortical tumor) were treated with ketoconazole at a dosage of 15 mg/kg given every 12 hours for a half month to 12 months. The disease in 2 dogs with pdh failed to respond to treatment, but 18 dogs had complete resolution of clinical signs of hyperadrenocorticism and significant (P &lt; 0.05) reduction in plasma cortisol responsiveness to exogenous adrenocorticotropin (acth). The healthy control dogs had a mean baseline plasma cortisol concentration of 1.4 ± 0.4 µg/dl and a post-acth cortisol concentration of 10.6 ± 3.1 µg/dl. Before ketoconazole administration, all 11 dogs with pdh had a mean baseline plasma cortisol concentration of 4.4 ± l.9 µg/dl and a post-acth cortisol concentration of 33.6 ± 17.6 µg/dl. The 9 dogs with adrenocortical tumor had a mean baseline plasma cortisol concentration of 4.4 ± 1.3 µg/dl and post-acth cortisol concentration of 28.1 ± 14.1 µg/dl. After 5 days of ketoconazole administration, the post-acth plasma cortisol concentration for dogs with pdh or adrenocortical tumor was 4.0 ± 5.4 µg/dl and 6.0 ± 3.3 µg/dl, respectively. Similar responses were observed after 60, 180, and 360 days of ketoconazole treatment.

Pituitary and adrenocortical responses to corticotropin-releasing factor in pigs

SUMMARY A study was conducted to determine whether differences in adrenocortical response to exogenous adrenocorticotropin (acth) were an accurate reflection of an animal's perception of and response to stressful stimuli, or whether the pituitary gland might modulate adrenocortical responsiveness. Sixteen Large White × Landrace female pigs, of which 8 had high adrenocortical response to acth and the other 8 had low response, were administered iv a bolus of synthetic human corticotropin-releasing factor (hcrf) at dose rates ranging from 0.002 to 2 μg/kg of body weight. Blood samples were collected at known times for up to 2 hours after administration of hcrf. Plasma acth and cortisol concentrations were measured by radioimmunoassay. Results indicate that hcrf stimulated the pituitary gland of high- and low-responding pigs to secrete acth, which in turn stimulated the adrenal cortex to secrete cortisol. Plasma acth concentration, before or after hcrf administration, was not significantly different between the high and low responders. However, high-responding pigs had higher cortisol concentration after hcrf administration than did low-responding pigs. Thus, the differences in adrenocortical response to acth between the 2 groups of pigs were not attenuated by variation in pituitary response. It is concluded that adrenocortical responsiveness to acth is an accurate indicator of the perception of and the response to stress.

Some effects of repeated handling on stress responses in sheep

Repeated exposure to a handling treatment was investigated as a possible method of reducing the stress response to shearing. Sheep were exposed to sham shearing (a procedure in which no wool is removed, but which otherwise resembles shearing) on four occasions at two-week intervals. The peak cortisol response to this procedure was not affected, but concentrations of plasma cortisol declined more rapidly to lower baseline concentrations after four exposures. Basal haematocrit also declined over the four exposures. In contrast, adrenal responsiveness to exogenous adrenocorticotrophic hormone (ACTH) increased over the period of sham shearing. The response to sham shearing was unrelated to flight distance of sheep or their position in a forced movement order. Flight distances of sham-shorn sheep were significantly shorter than those of control sheep after the four exposures. There was no correlation between forced movement or competitive order before and after sham shearing. The stress response to sham shearing was only slightly reduced by repetition, although the response apparently remained sufficient to affect adrenal responsiveness.

Adrenocortical Function in Prostatic Cancer Patients: Effects of Orchidectomy or Different Modes of Estrogen Treatment on Basal Steroid Levels and on the Response to Exogenous Adrenocorticotropic Hormone

Basal serum levels and ACTH-induced increments ('delta-values') of dehydroepiandrosterone (DHA) and its sulfate (DHAS), 4-androstene-3,17-dione (A-4), 17 alpha-hydroxyprogesterone (17-OHP), cortisol and testosterone and serum albumin levels were studied in patients with prostatic cancer before treatment and after orchidectomy or during estrogen treatment (intramuscular polyestradiol phosphate during the first 3 months, followed by another 3 months with additional oral ethinyl estradiol). Orchidectomy as well as single drug intramuscular or oral + intramuscular estrogens exerted a similar suppressive effect on basal levels of A-4 and 17-OHP. Orchidectomy caused a slight decrease in basal DHAS, while combined oral + intramuscular estrogens caused a pronounced decrease in basal DHAS and also in DHA. Single drug intramuscular estrogens did not affect basal DHA or DHAS levels. Increased basal cortisol levels appeared during combined oral + intramuscular estrogen therapy. delta DHA and delta A-4 values were unaffected by endocrine treatment, but delta 17-OHP and delta cortisol increased slightly after orchidectomy and during estrogen therapy. Significantly decreased albumin levels were only observed during combined oral + intramuscular estrogen treatment. Determination of estriol, which is a major metabolite of estradiol originating from polyestradiol phosphate, revealed significantly higher estriol levels during combined oral + intramuscular estrogen treatment than during single drug intramuscular estrogen therapy, indicating an increased induction of hepatic 16 alpha-hydroxylase activity. The pronounced decreases in DHAS and also in DHA during combined oral + intramuscular estrogen treatment are probably another reflexion of the liver side effects of oral estrogens.

Effect of stressor intensity on habituation and sensitization of glucocorticoid responses in rats.

This experiment was designed to study the effect of stressor intensity on habituation/sensitization of the adrenocortical stress response in rats. Rats were given 18 shocks in 3-hr daily sessions for 8 days, and a single shock probe before the sessions was used to determine how adrenocortical responsiveness changed with repeated exposure to the stress sessions. When lower intensity shock was given, the changes in plasma corticosterone response to shock probes followed a U-shaped curve--with a response that first habituated to no-shock control levels but later returned to the same magnitude as seen on the 1st probe day. Plasma corticosterone responses in rats given higher intensity shock never habituated and instead demonstrated an increased response indicative of sensitization; a temporal delay of 1 week occurred before sensitization developed. Responsiveness to exogenous adrenocorticotropin 24 hr after the last stress session was monotonically related to the intensity of the stressor presented during the experimental sessions. These data are consistent with the rule from the habituation literature that stimulus intensity is inversely related to the magnitude of habituation. Thus the data extend the dual process theory of Groves and Thompson (1970) to an endocrine respondent. The data also suggest that an explanation as to discrepancies in the literature concerning adrenocortical response to repeated presentation of stressors may relate to differences in the stressor parameters used.

Research Note: Physiological Effects of Adrenocorticotropic Hormone and Hydrocortisone in Laying Hens

To study the hormonal effects on hematologic parameters as indicators of chronic stress, exogenous adrenocorticotropin (ACTH) at 6.3 or 20.0 IU/kg/day and hydrocortisone at .25 or 2.5 mg/kg/day were administered parenterally to laying hens. Both ACTH treatments induced significant (P<.05) heterophilia, monocytosis, eosinophilia, and basophilia. Significantly elevated leucocyte counts and lymphopenia (P<.05) were observed with the high dosage of ACTH. Both hydrocortisone-treated groups developed an absolute lymphopenia and heterophilia (P<.05). The low dosage of hydrocortisone induced a significant (P<.05) monocytosis; the high dosage caused significant (P<.05) decreases in the total eosinophil and basophil counts as well as an increase in the ratio of heterophils to lymphocytes. The hemopoietic parameters, especially heterophil counts, were sensitive indicators of a hormonal stress response induced by the administration of ACTH and hydrocortisone.

Comparative effects of proligestone and megestrol acetate on basal plasma glucose concentrations and cortisol responses to exogenous adrenocorticotrophic hormone in cats

Cats were given megestrol acetate (MA, 5 mg once daily for 14 days), subcutaneous proligestone (PRG, 100 mg on two occasions one week apart) or subcutaneous saline (1 ml as for PRG). In cats given saline (n = 6) basal cortical concentrations, cortisol concentrations after adrenocorticotrophic hormone (ACTH) administration and fasting blood glucose concentrations did not change significantly during the following seven weeks. Cats given MA (n = 7) developed suppression of basal and ACTH-stimulated cortisol concentrations and fasting hyperglycaemia during treatment. Effects on cortisol persisted for two weeks after MA dosage ceased. In cats given PRG (n = 7), basal cortisol concentrations were reduced overall, but only three cats had persistently suppressed post-ACTH cortisol concentrations. Adrenal suppression continued for 14 weeks in one of these and for at least 22 weeks in two cats. Fasting blood glucose concentrations were unchanged in PRG-treated cats.

PITUITARY‐ADRENOCORTICAL ACTIVITY IN THE FETAL PIG IN THE LAST THIRD OF GESTATION

The responsiveness of the fetal adrenal to a rise in either endogenous or exogenous ACTH (adrenocorticotrophic hormone) was examined acutely in piglets between 70 and 105 days gestation (term, 115 days). In addition the pre-partum changes in plasma ACTH and cortisol were followed in chronically catheterized fetuses and the effect of a continuous intrafetal ACTH infusion on the time of delivery was also investigated. The acute experiments on ten sows were carried out (under sodium pentobarbitone) on twenty-five fetuses, sampled from a branch of the umbilical artery with minimal disturbance. A second sample was taken 10-20 min later after exteriorization or surgery (catheterization). Such fetal manipulation resulted in significant increases in plasma ACTH and cortisol from 70 days gestation and the responses increased with fetal age. No corresponding changes were seen in the controls or in the sow over the same period. An exogenous bolus of ACTH (200 ng ml-1 I.V.) evoked rises in fetal plasma cortisol comparable with the endogenous changes (+11 +/- 2 ng ml-1, n = 4). Chronic experiments were carried out on fourteen sows catheterized under sodium pentobarbitone anaesthesia at 95-100 days gestation; in fetuses sampled until delivery (at 111-114 days) gradual rises in both fetal plasma cortisol and ACTH were observed. There was a highly significant positive correlation between plasma cortisol and log plasma ACTH (r = 0.81, n = 52, P less than 0.001). Analysis of the basal values from the 70-100 day fetuses also showed a positive correlation (r = 0.47, n = 23, P less than 0.05) but the slope of the regression line was significantly less than that for the older fetuses indicating a greater adrenocortical response to a given level of ACTH nearer term. In five sows a continuous infusion of ACTH (0.125 mg day-1 for 4-5 days from about 100 days) was given to one or two fetuses per litter (total size, 7-12). This treatment resulted in a rise in fetal plasma cortisol to 85.4 +/- 8.9 ng ml-1, which was equivalent to that found during labour, but did not induce premature parturition.

Ontogeny of Daily Rhythmicity in Plasma Corticosterone and Variation in Sensitivity of the Corticosterone Response in Turkey Poults

Two trials were conducted with turkey poults to examine the ontogeny of daily rhythmicity of plasma corticosterone (CS), and to determine the plasma CS response to adrenocorticotropic hormone (ACTH) injections and temperature stress at different times during a light-dark cycle. In Trial 1, CS levels were determined at 3-h intervals over a 24-h period in 3, 10, and 14-day-old tom and hen poults maintained on a 12 h light:12 h dark (12L:12D) light-dark cycle. Plasma CS levels of tom and hen poults were similar. A robust daily rhythm in plasma CS occurred by 10 days of age, with maximal levels of CS occurring during the scotophase.In Trial 2, daily variation in plasma CS sensitivity to cold treatment or ACTH in 2-wk-old toms was examined. Tom poults were exposed to cold water immersion (5 C for 1 min), porcine ACTH injection (1 IU/kg), or saline injection at 1100 h in midphotophase and at 2300 h in midscotophase. Treatments significantly increased plasma CS in both the photophase and scotophase, with the levels being significantly higher in the scotophase. At midphotophase cold or ACTH treatment induced, respectively, a 489 and 546% increase in plasma CS above that of controls. During midscotophase, 746 and 695% increases in CS above levels for controls were induced by cold stress or ACTH, respectively. Differences between percent changes for times of day were not significantly different.It was concluded that a daily rhythm in plasma CS in turkey poults grown under a 12L:12D light-dark cycle occurs between 3 and 10 days of age, with maximum levels occurring during the scotophase. A daily variation in the adrenal cortical response to exogenous ACTH or cold water treatment in excess of the normal plasma CS rhythm was not apparent.