Mean Adrenocorticotropic Hormone Research Articles

Stress Parameters of Horse Riders in Kök-Börü Games by Winning and Losing Situations

ABSTRACT Introduction This study examined the effects of winning or losing situations on the stress, metabolic, and physiological aspects of horse riders in Kök-Börü, a traditional equestrian team game. Methods Blood samples were collected from the riders of four different teams participating in two separate Kök-Börü games, both before and after gameplay. The samples were examined for levels of cortisol, adrenocorticotropic hormone (ACTH), beta-endorphin, adrenaline, noradrenaline, triiodothyronine (T3), and thyroxine (T4) using species-specific commercial enzyme-linked immunosorbent assay kits. The same samples were tested for biochemical and hematological parameters with an autoanalyzer. Results Post-game, the riders from the winning teams showed an increase in the serum levels of white blood count, granulocytes (GRA), percent GRA, mean corpuscular volume, platelet count, plateletcrit, creatine kinase, albumine, aspartate transferase, creatine, cortisol, and ACTH compared to their levels before the game. In contrast, the post-game serum levels of lymphocytes, adrenaline, noradrenaline, and T3 of the winning team were lower. When the pre-game samples of winning and losing teams were compared, it was observed that sodium and T4 levels were higher in the winners. Conclusions The data suggest that winning team riders put in more effort and experienced more stress. Conversely, those on losing teams exerted less effort and experienced less stress, as indicated by the parameter changes.

Hypothalamic-Pituitary-Adrenal Axis Recovery Following the 1-mg Overnight Dexamethasone Suppression Test in Healthy Volunteers.

BackgroundThe recovery of hypothalamic-pituitary-adrenal (HPA) axis suppression following pharmacological doses of various steroids has been studied previously. However, no study has been conducted using the more commonly used 1-mg dexamethasone in the overnight dexamethasone suppression test (ODST). Hence, we aimed at evaluating HPA axis recovery after the 1-mg ODST.ObjectivesThis study aimed at investigating the pattern and time of recovery of the HPA axis following the 1-mg ODST in healthy subjects.MethodsTen healthy volunteers aged 18 - 40 years, BMI < 30 kg/m2, with neither exposure to steroids nor interfering drugs were included. The 1-mg ODST was performed, and the adrenocorticotropic hormone (ACTH) and cortisol samples were withdrawn at regular intervals. The serum cortisol of < 1.8 µg/dL was considered as HPA axis suppression, whereas the cortisol value equal to or more than baseline was deemed as recovery.ResultsCortisol and ACTH levels were suppressed in all subjects 9 hours following the 1-mg ODST. Although ACTH showed an early increase after 8 hours, the upsurge was noticed following 24 hours (mean ± SD, 34.42 ± 18 pg/mL). Later, cortisol accompanied ACTH, and both reached their baseline after 72 hours (mean ± SD, ACTH, 37.48 ± 12.44 pg/mL; cortisol, 8.45 ± 3.32 μg/dL). A small dip in ACTH and cortisol (mean ACTH, 23.84 pg/mL; mean cortisol, 2.3 μg/dL) was observed after 24 - 36 hours indicating the return of the diurnal rhythm before complete recovery.ConclusionsThe complete recovery of the HPA axis occurs only 72 hours following the 1-mg ODST. ACTH begins to recover as early as 8 hours after the maximal suppression and diurnal rhythm of ACTH and cortisol resume 24 to 36 hours later.

Circannual variability in adrenocorticotropic hormone responses to administration of thyrotropin-releasing hormone in clinically normal horses in Australia

Thyrotropin releasing hormone (TRH)-stimulation testing for pituitary pars intermedia dysfunction (PPID) in horses is only recommended at certain times of the year. Current diagnostic cut-off values reflect testing in the northern hemisphere during this time. The aims of this study were to evaluate TRH stimulation testing during two different phases of the circannual pituitary cycle and to determine whether diagnostic cut-off values developed in the northern hemisphere are appropriate in Australia. Thirteen clinically normal horses at Perth, Western Australia, and 23 horses at Townsville, Queensland, Australia, had TRH stimulation tests performed at two different time points during the circannual pituitary cycle. At both locations, post-TRH adrenocorticotropic hormone (ACTH) concentrations were significantly different between testing time points (Perth: P=0.001; Townsville: P<0.0001). In Perth, the mean ACTH concentrations 10min post-TRH in September and March were 51.4pg/mL (95% confidence interval, CI, 46.4–56.4pg/mL) and 248.5pg/mL (95% CI 170.2–326.9pg/mL), respectively. The median percentage change in ACTH concentrations in March was 361.9%. In Townsville, the mean ACTH concentrations 30min post-TRH in September and April were 35.3pg/mL (95% CI 29.6–40.9pg/mL) and 112.3pg/mL (95% CI 93.4–131.2pg/mL), respectively. The median percentage change in ACTH concentrations in April was 144.7%. The ACTH cut-off value after TRH stimulation in normal horses in September in Perth and Townsville was similar to the values established in the northern hemisphere. However, TRH stimulation testing in March/April was highly variable at both locations.

Performance of low-dose cosyntropin stimulation test handled via plastic tube.

Studies on 1 μg low-dose test showed that among 1 μg cosyntropin samples pushed through long IV plastic tubing, some adrenocorticotropic hormone dosage was not recovered, and in healthy volunteers it provided subnormal cortisol responses. The aim of the current study is to assess whether there is any loss in adrenocorticotropic hormone 1-24 concentration when pushed through a short plastic tube, and to assess serum and salivary cortisol responses in low-dose test among healthy volunteers, using a similar short plastic tube vs. direct intravenous consyntropin injection. We evaluated in vitro if adrenocorticotropic hormone was absorbed in a 2.5 cm plastic tube by measuring adrenocorticotropic hormone 1-24 concentration in a 1 μg/ml adrenocorticotropic hormone aliquot solution before and after being flushed through the plastic tube. For the in vivo study, we recruited 20 healthy adult volunteers. Each subject underwent low-dose test via 2.5 cm plastic tube via plastic tube and via direct intravenous injection by a metal syringe via direct intravenous injection, and cortisol responses were determined. Mean adrenocorticotropic hormone 1-24 concentration did not differ significantly when flushed via plastic tube or measured in the aliquot solution (P = 0.25). In vivo, mean 30-min serum cortisol concentrations were 20.47 ± 2.87 and 21.62 ± 3.89 μg/dl in via plastic tube and in via direct intravenous injection tests, respectively, and did not show a significant difference (P = 0.16). In low-dose test, using a 2.5 cm plastic tube ensures completeness of the intravenous adrenocorticotropic hormone injection dosage and provides equivalent cortisol responses.

More than hormones: Sex differences in cardiovascular parameters after sleep loss in rats

Although the influence of sex on sleep pattern and cardiovascular parameters is well known, knowledge regarding the effects of sleep loss on heart responses in both sexes is scarce. The present study investigated the effects of paradoxical sleep deprivation (PSD) and chronic sleep restriction (SR) on cardiovascular parameters and adrenocorticotropic hormone (ACTH) levels in male and female rats. Both groups were randomly assigned to PSD for 96 h, SR for 21 days or home-cage control. Mean arterial pressure (MAP), heart rate (HR), baroreflex sensitivity (bradycardia and tachycardia responses) and ACTH levels were evaluated. The results showed that PSD induced a significant increase in HR and ACTH levels in both sexes, although male rats presented higher levels of ACTH hormone compared to females. In addition to sex-specific responses, PSD decreased the tachycardia only in male rats. SR, induced a significant increase in MAP and decrease in bradycardia in both sexes. Male rats were more affected by sleep deprivation protocols than females for MAP, bradycardia response, and ACTH levels. The results showed that the effects of sleep loss on cardiovascular parameters are associated with the protocol of sleep deprivation and that sex can modulate these effects. We suggested this experimental model as a suitable tool for further investigations of the relationship between cardiovascular parameters and sleep.

Effects of ghrelin, growth hormone–releasing peptide–6, and growth hormone–releasing hormone on growth hormone, adrenocorticotropic hormone, and cortisol release in type 1 diabetes mellitus

In type 1 diabetes mellitus (T1DM), growth hormone (GH) responses to provocative stimuli are normal or exaggerated, whereas the hypothalamic-pituitary-adrenal axis has been less studied. Ghrelin is a GH secretagogue that also increases adrenocorticotropic hormone (ACTH) and cortisol levels, similarly to GH-releasing peptide–6 (GHRP-6). Ghrelin's effects in patients with T1DM have not been evaluated. We therefore studied GH, ACTH, and cortisol responses to ghrelin and GHRP-6 in 9 patients with T1DM and 9 control subjects. The GH-releasing hormone (GHRH)–induced GH release was also evaluated. Mean fasting GH levels (micrograms per liter) were higher in T1DM (3.5 ± 1.2) than in controls (0.6 ± 0.3). In both groups, ghrelin-induced GH release was higher than that after GHRP-6 and GHRH. When analyzing Δ area under the curve (ΔAUC) GH values after ghrelin, GHRP-6, and GHRH, no significant differences were observed in T1DM compared with controls. There was a trend ( P = .055) to higher mean basal cortisol values (micrograms per deciliter) in T1DM (11.7 ± 1.5) compared with controls (8.2 ± 0.8). No significant differences were seen in ΔAUC cortisol values in both groups after ghrelin and GHRP-6. Mean fasting ACTH values were similar in T1DM and controls. No differences were seen in ΔAUC ACTH levels in both groups after ghrelin and GHRP-6. In summary, patients with T1DM have normal GH responsiveness to ghrelin, GHRP-6, and GHRH. The ACTH and cortisol release after ghrelin and GHRP-6 is also similar to controls. Our results suggest that chronic hyperglycemia of T1DM does not interfere with GH-, ACTH-, and cortisol-releasing mechanisms stimulated by these peptides.

The acute effects of a mineralocorticoid receptor (MR) agonist on nocturnal hypothalamic–adrenal–pituitary (HPA) axis activity in healthy controls

Both glucocorticoid and mineralocorticoid receptors (GRs and MRs) help modulate cortisol feedback on the hypothalamic-adrenal-pituitary (HPA) axis. In brain, MRs inhibit the HPA axis and are thought to be fully occupied. Thus, prior studies of the effects of an MR agonist on HPA axis activity have first used metyrapone to inhibit cortisol production and to consequently deplete the receptors. Herein, we propose that an MR agonist may inhibit the HPA axis without first "unloading" receptors of endogenous cortisol. Healthy subjects were admitted to the General Clinical Research Center. Blood was sampled for cortisol and adrenocorticotropic hormone (ACTH) from 16:00 to 24:00 h, when greatest MR activity is expected, on two consecutive nights. The first night established a baseline and the second night established response. On the second afternoon, all subjects were given 0.5mg fludrocortisone. Mean cortisol and ACTH were computed from 16:00 to 24:00 h. Fludrocortisone acutely decreased mean cortisol (p=0.003; effect size (ES) 1.65) and mean ACTH (p=0.000, ES 4.46). Additionally, post hoc analysis showed that fludrocortisone tended to decrease the cortisol/ACTH ratio (p=0.0686, ES 0.92) across the same time period. Fludrocortisone significantly inhibits nocturnal HPA axis activity without first depleting MR receptors with metyrapone. This suggests that brain MRs are not fully occupied by endogenous cortisol and can be further activated by an agonist. The decrease in cortisol/ACTH ratio suggests a possible role on adrenal sensitivity as well. The ability to lower nocturnal HPA axis activity has interesting implications in disorders of HPA axis excess, such as insomnia, depression and healthy aging.

Assessment of Insulin Resistance in the Idiopathic Hirsutism

Background: Idiopathic hirsutism (IH) is the second most common cause of hirsutism, after polycystic ovary syndrome and occurs in about 15% of hirsute women. There are not many studies showing whether patients with IH also have insulin resistance. In the present study, we aimed to investigate the insulin sensivity in IH with non-obese and changing hormone levels during the hyperinsulinemic-euglycemic clamp. Methods: Twenty (20) non-obese women with IH (Group I) ranging in age from 20 to 30 (mean 25 ± 5) years were studied. Hirsutism in women with normal testosterone (T) levels and regular menstrual cycles is as defined IH. Twenty (20) healthy women (mean age 23 ± 2 years) (Group II) were included in this study as the control group. Insulin sensitivity was assessed with modified euglycemic insulin clamp technique. Samples of prolactin, luteinizing hormone (LH), follicle-stimulating hormone, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate, cortisol, estradiol, progesterone, 17-OH progesterone (17-OHP), total T, and free T (FT) were obtained at baseline and at 2nd hour during clamp. Results: Steady-state (120 min) glucose disposal rates were higher in Group II than Group I (7.51 ± 0.83 vs. 5.76 ± 1.89 mg/kg/min). Mean FT, ACTH, cortisol, LH, prolactin and 17-OHP levels were found to have decreased statistically significantly (p < 0.05) in Group I. Mean FT, ACTH, and prolactin levels were found to have decreased statistically significantly (p < 0.05) in Group II during the clamp. Mean baseline levels of FT, LH and prolactin were greater in women with hirsutism than in the control subjects (p < 0.05). Insulin mediated glucose disposal was lower in the normal weight women with IH than in those without hirsutism. Conclusions: Mean FT, 17-OHP and dehydroepiandrosterone sulfate levels decreased during euglcemic-hyperinsulinemic clamp in IH.

Long-term anti-tumor necrosis factor antibody therapy in rheumatoid arthritis patients sensitizes the pituitary gland and favors adrenal androgen secretion.

New insights into the role of tumor necrosis factor (TNF) in the pathogenesis of rheumatoid arthritis (RA) have expanded our understanding about the possible mechanisms by which anti-TNF antibody therapy reduces local synovial inflammation. Beyond local effects, anti-TNF treatment may modulate systemic antiinflammatory pathways such as the hypothalamic-pituitary-adrenal (HPA) axis. This longitudinal anti-TNF therapy study was designed to assess these effects in RA patients. RA patients were given 5 infusions of anti-TNF at weeks 0, 2, 6, 10, and 14, with followup observation until week 16. We measured serum levels of interleukin-6 (IL-6), adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17[OH]progesterone), cortisol, cortisone, androstenedione (ASD), dehydroepiandrosterone (DHEA), and DHEA sulfate in 19 RA patients. Upon treatment with anti-TNF, we observed a fast decrease in the levels of serum IL-6, particularly in RA patients who did not receive parallel prednisolone treatment (P = 0.043). In these RA patients who had not received prednisolone, the mean serum ACTH levels sharply increased after every injection of anti-TNF, which indicates a sensitization of the pituitary gland (not observed for the adrenal gland). During treatment, the ratio of serum cortisol to serum ACTH decreased, which also indicates a sensitization of the pituitary gland (P < 0.001), and which was paralleled by constant cortisol secretion. The adrenal androgen ASD significantly increased relative to its precursor 17(OH)progesterone (P = 0.013) and relative to cortisol (P = 0.009), which indicates a normalization of adrenal androgen production. The comparison of patients previously treated with prednisolone and those without previous prednisolone revealed marked differences in the central and adrenal level of this endocrine axis during long-term anti-TNF therapy. Long-term therapy with anti-TNF sensitizes the pituitary gland and improves adrenal androgen secretion in patients who have not previously received prednisolone treatment. These changes are indicative of normalization of the HPA axis and must therefore be considered as evidence of an additional antiinflammatory influence of anti-TNF treatment in patients with RA.

Endogenous alpha-MSH modulates the hypothalamic-pituitary-adrenal response to the cytokine interleukin-1beta.

We and others have previously shown that exogenous alpha-MSH antagonizes the stimulatory effects of the cytokine interleukin (IL)-1 on the hypothalamic-pituitary-adrenal (HPA) axis. It is currently unknown, however, if endogenous alpha-MSH plays a physiological role in regulating the HPA response to IL-1. We have therefore examined the HPA response to IL-1beta in rats pretreated with an affinity purified alpha-MSH antiserum (AS) infused intracerebroventricularly to neutralize endogenous alpha-MSH within the brain. alpha-MSH AS or a similarly purified fraction of normal rabbit serum (NRS) was injected intracerebroventricularly at 16 h and at 1 h prior to the i.c.v. injection of IL-1beta (2 ng or 20 ng) and blood samples were collected through an indwelling atrial catheter. After 2 ng IL-1beta, the adrenocorticotropic hormone (ACTH) response was significantly greater in the alpha-MSH AS treated rats (n = 7) compared to the NRS treated rats (n = 7) (P <0.01); the mean ACTH level rose to a peak of 594+208 pg/ml in the alpha-MSH AS treated rats vs 274+/-122 pg/ml in the NRS treated rats. The area under the ACTH response curve in the alpha-MSH AS treated animals was 181% of that in the NRS treated animals (P<0.05). A significant effect of alpha-MSH AS on the corticosterone response to i.c.v. IL-1beta was also noted during the first 3 h of the study (P<0.05). The mean area under the corticosterone response curve for the first 3 h in the alpha-MSH AS treated animals was 144% of that in the NRS treated animals (P <0.05). After 20 ng IL-1beta, the ACTH response over time was again significantly greater in the alpha-MSH AS treated rats (n=8) compared to the NRS treated rats (n=9) (P<0.02); the mean ACTH level rose to a peak of 673+/-190 pg/ml after alpha-MSH AS vs 490+/-115 pg/ml after NRS. Corticosterone levels rose to a peak of 42+/-3.9 microg/dl in the alpha-MSH AS treated rats vs 37+/-4.6 microg/dl in the NRS treated rats; this difference was not significant. We conclude that the IL-1beta induced stimulation of ACTH is significantly enhanced by antagonizing the activity of alpha-MSH. These results support a physiological role for endogenous alpha-MSH in limiting the HPA response to this inflammatory cytokine.

Release of plasma atrial natriuretic peptide after volume expansion is not related to pituitary-adrenal axis diurnal variation in normal subjects.

The existence of a circadian rhythm of atrial natriuretic peptide (ANP) in humans is controversial. We studied the plasma ANP response to isotonic blood volume expansion in the morning and in the afternoon and its relationship with adrenocorticotropic hormone (ACTH)-cortisol diurnal variation in seven normal subjects. Basal plasma ANP level was similar in the morning (19.6 +/- 2.4 pg/ml) and in the afternoon (21.8 +/- 4.8 pg/ml). The ANP peak obtained with saline infusion (0.9% NaCl, 12 ml/kg) in the morning (49.4 +/- 8 pg/ml) did not differ from that obtained in the afternoon (60.3 +/- 10.1 pg/ml). There was no correlation between the individual mean cortisol and ACTH levels and the ANP peak obtained with saline infusion. These data indicate no diurnal variation in plasma ANP secretion induced by blood volume expansion and no relationship between plasma ANP peak and ACTH-cortisol diurnal variation.

Ontogeny and ultradian rhythms of adrenocorticotropin and cortisol in the late-gestation fetal horse

Fetal maturation and the timing of parturition in both sheep and primates are thought to be controlled by the hypothalamic-pituitary-adrenal axis but little is known about the endocrinology of the equine fetus. We investigated the ontogeny of plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol and corticosteroid binding capacity in the late-gestation fetal horse. We also wished to determine whether there is ultradian rhythmic release of ACTH and cortisol in fetal horses and we compared fetuses to maternal and non-pregnant adult horses. Six fetuses, 278-304 days gestation (term approximately 335), were catheterized and sampled daily until delivery. Mean (+/- S.E.M.) ACTH concentrations increased significantly from 159 +/- 21 to 246 +/- 42 pg/ml over the last 2 days before parturition. Fetal cortisol increased significantly from 3.1 +/- 1.0 to 13.4 +/- 3.7 ng/ml (mean +/- S.E.M.) over the last 9 days before delivery. The slope of regressions for ACTH and cortisol concentrations with respect to time were positive in all subjects and statistically significant in 3 of 6 for ACTH and 5 of 6 for cortisol. Fetal corticosteroid binding capacity declined from 49.5 +/- 20.5 to 16.1 +/- 2.2 ng/ml (mean +/- S.E.M.) over the last 10 days before parturition. However, the greatest changes in ACTH, cortisol and corticosteroid binding capacity occurred very late in gestation, during the last 48 to 72 h before parturition.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of academic stress and season on 24-hour mean concentrations of ACTH, cortisol, and β-endorphin

We investigated the influence of a common stressful event, i.e., academic examinations, on the 24-h mean concentration of adrenocorticotropic hormone (ACTH), cortisol, and/or beta-endorphin. In addition, we evaluated the effect of season on the endocrine response to this stressor. We studied medical students (n = 55), screened for a variety of health and life style factors, from three consecutive medical school classes 1 month before, during, and 2 weeks following examinations. Hourly blood samples were obtained from an indwelling catheter and two serum pools were made (0800-2200h = day and 2300-0700h = night). Examinations produced a significant (p < .001) increase in perceived stress scores. In addition, we found a significant (p < .001) effect of examination stress on the increase in mean daytime but not nocturnal ACTH levels during autumn, but not during the spring. In contrast, the examination stress did not significantly affect day or night mean cortisol levels from baseline to examination week. We further divided the students by whether their perceived stress scores increased during examination week and fell during recovery (Group 1) or whether their perceived stress scores did not follow the expected pattern (Group 2). We found that in the Group 1 students who perceived the most stress, cortisol levels significantly increased (p < .001) from baseline to examination. Therefore, the nature of the stressor and the state of the responder were of equal importance in the observed cortisol response during examinations among these students. Further, academic stress had no significant effect on beta-endorphin levels. Finally, we found that the mean day and night ACTH levels were higher (p < .001) in the spring than in the fall; a seasonal influence on cortisol and beta-endorphin concentrations, however, was not observed. In summary, we have demonstrated that stress associated with the taking of examinations produces a dissociation among mean 24-h levels of ACTH, cortisol, and beta-endorphin. In addition, daytime cortisol levels increased during examinations only in the group of students whose perceived stress scores increased. Further, a seasonal influence on ACTH secretion was suggested by these results with higher levels observed in the spring than in the fall.

Coincident plasma ACTH and corticosterone time series: Comparisons between young and old rats

Senescence is accompanied by a reduced ability to respond to a variety of physical and behavioral stressors. A sizable literature has been devoted to the interplay between hypothalamic-pituitary-adrenocortical axis dysfunction and senescence; yet, the precise interactions remain an enigma. Adrenocorticotropic hormone (ACTH) is secreted in pulsatile bursts generating complex signals in the plasma compartment that must be “read” by adrenocortical cells in order to initiate appropriate secretory responses. We have previously demonstrated subtle differences between young and old rats in the pattern of fluctuations in plasma ACTH concentrations over time, despite no difference in mean levels. The present work addressed the physiological significance of these differences in the plasma ACTH signal by analyzing the corresponding plasma corticosterone concentration time series and the relationship between these two hormones over time. Time series of integrated 10-min ACTH and corticosterone concentrations were collected over 4 h at the time of diurnal activation and analyzed in the time and frequency domains. The time of onset of the diurnal surge occurred 20 min later in old rats, and the ratio of corticosterone to ACTH was less at the time of onset and peak of the diurnal surge. Corticosterone levels were lower in old rats and mean ACTH and corticosterone levels were correlated in young but not old rats, as were maximum levels of the two hormones. Cross-correlation of ACTH and corticosterone time series and comparison of spectra were consistent with smoother fluctuations in plasma corticosterone in old animals with less variability at time scales less than 55 min. We conclude that age may be associated with a delay in diurnal activation of the HPA axis, a loss of sensitivity of adrenal corticosterone secretion to plasma ACTH levels, and a relative loss of high frequency variability in the corticosterone signal, as seen in many physiological systems with age.

Corticotropin responses to hypoglycemia and hypotension during ovine pregnancy.

The adrenocorticotropic hormone (ACTH) responses to hypoglycemia and to hypotension were compared in pregnant and nonpregnant ewes. In the first study pregnant and nonpregnant ewes were each subjected to hypoglycemia induced by injection of 0.05, 0.10, or 0.25 U regular insulin/kg body wt or to saline infused as a control. In the second study pregnant and nonpregnant ewes were subjected to hypotension induced by the infusion of 2.5, 5.0, or 10.0 micrograms nitroprusside.kg-1.min-1 or to dextrose infused as a control. ACTH responses to hypoglycemia were significantly increased in the pregnant ewes, and the relation between plasma glucose and plasma ACTH was shifted to the right, indicating greater ACTH responses for a given level of hypoglycemia in the pregnant state. The mean ACTH response to infusion of nitroprusside was reduced during pregnancy, despite significantly lower mean arterial blood pressure in the pregnant ewes. When the relation between mean arterial pressure and ACTH was compared in the two groups of ewes, the relation was significantly shifted to the left in the pregnant ewes, indicating lower ACTH responses to a given level of pressure during pregnancy. The results suggest that pregnancy does not uniformly alter ACTH responses to stimuli, suggesting multiple, stimulus-specific effects of pregnancy on the hypothalamo-pituitary-adrenal axis.

A characterization of hypothalamic-pituitary-adrenal axis function during and after human cardiac arrest.

This study characterizes hypothalamic-pituitary-adrenal axis function during cardiopulmonary arrest and after return of spontaneous circulation. Prospective case series. A large urban emergency department and intensive care unit over an 8-month period. Two hundred five adult patients presenting in cardiopulmonary arrest to an urban emergency department. Three patients known to be taking corticosteroids were excluded from the study. Cortisol concentrations were measured before and after advanced cardiac life support and for five consecutive hours after return of spontaneous circulation. Adrenocorticotropic hormone (ACTH) concentrations were measured before advanced cardiac life support and when the cosyntropin stimulation tests were performed 6 and 24 hrs after the return of spontaneous circulation. The mean initial serum cortisol concentration was 32.0 +/- 33.1 micrograms/dL (882.9 +/- 913.2 nmol/L). Fifty-three percent of patients had cortisol concentrations of < 20 micrograms/dL (< 552 nmol/L) at the end of cardiac arrest. Among 44 patients who achieved return of spontaneous circulation, 98% had initial cortisol concentrations of > 10 micrograms/dL (> 276 nmol/L) and 73% of patients had initial cortisol concentrations of > 20 micrograms/dL (> 552 nmol/L). Mean serum cortisol concentrations increased significantly (p = .0001) from 1 to 6 hrs after return of spontaneous circulation and decreased significantly (p = .03) from 6 to 24 hrs. A serum cortisol concentration of < 30 micrograms/dL (< 828 nmol/L) was associated with a 96% and 100% mortality rate at 6 and 24 hrs, respectively. Mean ACTH concentrations were increased without a significant difference between the initial and 6-hr concentrations. Mean ACTH concentrations decreased between 6 and 24 hrs (p = .06). There were no significant responses to the cosyntropin stimulation at 6 and 24 hrs. Cortisol concentrations after out-of-hospital cardiac arrest are lower than those concentrations reported in other stress states. There is an association between cortisol concentrations and short-term survival after cardiac arrest. Survivors have a significantly greater increase in serum cortisol concentrations than nonsurvivors during the first 24 hrs. Lower than expected cortisol concentrations for the extreme stress of cardiac arrest may have pathologic significance in the hemodynamic instability seen after return of spontaneous circulation. The etiology of the low cortisol concentrations may be primary adrenal dysfunction.

Domperidone treatment enhances corticotropin-releasing hormone stimulated adrenocorticotropic hormone release from the dog pituitary.

While dopamine (DA) is known to inhibit pituitary intermediate lobe proopiomelanocortin (POMC) peptide secretion and synthesis in most species, its influence on anterior-lobe (AL) POMC peptide synthesis and secretion is less clear. We, therefore, sought to determine the effects of daily treatment with the DA receptor antagonist, domperidone (DOM), on secretion of the POMC peptides adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) from the dog pituitary, and on concentrations of another pituitary hormone regulated by DA, prolactin (PRL). Dogs treated for 7 days with DOM had significantly higher peak ACTH concentrations in response to corticotropin-releasing hormone (CRH) injection (329 +/- 37 pg/ml, mean +/- SD) than did controls (164 +/- 42 pg/ml). PRL was also significantly (p < 0.05) increased in samples collected on a daily basis after DOM injections (9.5 +/- 4.6 vs. 4.3 +/- 3.3 ng/ml in controls). However, plasma alpha-MSH concentrations were unaffected by DOM. In a subsequent study, dogs were again treated daily with DOM or vehicle (controls), and additionally were given dexamethasone (DEX) to block AL ACTH release. DEX-treated controls showed low daily and CRH-stimulated ACTH and cortisol concentrations (generally below assay sensitivity). In contrast, DEX + DOM-treated dogs had daily mean ACTH concentrations ranging from 10 +/- 8.1 to 32 +/- 26 pg/ml and mean peak post-CRH ACTH concentrations of 174 +/- 16 pg/ml. Although daily cortisol concentrations were below assay sensitivity, the mean peak post-CRH cortisol concentration was 6.7 +/- 1.8 micrograms/dl, indicating that the immunoreactive ACTH was biologically active.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsatile ACTH and cortisol in goats: effects of insulin-induced hypoglycemia and dexamethasone.

Insulin-induced hypoglycemia is a metabolic stress that stimulates secretion of adrenocorticotropic hormone (ACTH) and cortisol in a number of animal species. Dexamethasone is a potent synthetic glucocorticoid that suppresses the secretion of ACTH and cortisol. Both ACTH and cortisol exhibit complex secretory patterns demonstrating ultradian and circadian rhythms. This work investigated the pattern of ACTH and cortisol response to hypoglycemia in goats and the effect of dexamethasone on this response. Five goats were pretreated with dexamethasone (0.1 mg/kg) and 5 with saline. Blood samples were taken every 2 min for 60 min before and 60 min after administration of insulin (2.5 IU/kg, i.v.). Immunoreactive ACTH and cortisol were measured in all samples and glucose in selected samples. Data sets were analyzed for significant pulses with the Cluster Analysis program. Complete data sets were compared as well as those for each 30-min interval. Plasma glucose was lower than preinsulin levels at 10 min, declined rapidly between 10 and 30 min, and remained low 30-60 min after insulin injection in both treatment groups. Controls showed a rapid rise in ACTH and cortisol beginning 30 +/- 10 min postinsulin. The increase in mean plasma hormone levels during hypoglycemia was predominantly due to an increase in amplitude of secretory pulses for ACTH and cortisol compared with the 30 min before insulin. Dexamethasone significantly lowered mean ACTH and cortisol levels and prevented alteration in plasma ACTH and cortisol secretion during hypoglycemia but did not totally ablate pulsatile activity of either hormone. The amplitude of ACTH and cortisol pulses was significantly decreased by dexamethasone treatment. The frequency of cortisol but not ACTH pulses was also significantly decreased.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacodynamics of the antiprogesterone RU486 in women after oral administration

The pharmacokinetic characteristics of RU486 and its acute effects on anterior pituitary hormone secretion after oral administration were examined in six normal women. Serum RU486 concentrations were determined by a radioimmunoassay. The absorption of RU486 was rapid with peak serum levels reached approximately 90 minutes after a single oral dose (4 mg/kg). The disappearance of RU486 and its metabolites conformed to a noncompartmental model with a mean apparent half-life of 53.7 +/- 6.9 hours. The mean apparent volume of distribution and clearance rate were 1.47 +/- 0.25 l/kg and 1.04 +/- 0.09 1/hour, respectively. In comparison with a control group of normal women (n = 9), there were significant elevations in transverse mean cortisol levels in the RU486 group (P less than 0.01). However, mean adrenocorticotropic hormone (ACTH) levels and the diurnal pattern of ACTH and cortisol secretion were not changed. RU486 induced a mild prolactin (PRL) elevation (P less than 0.01), whereas thyroid-stimulating hormone (TSH) and luteinizing hormone (LH) levels were not altered. In view of the relatively slow clearance rate for RU486 and its metabolites, our findings suggest that the pharmacologic action of RU486 is prolonged after a single oral dose.

Correlation between plasma levels of ACTH and beta-endorphin in the first seven days of postnatal life.

Plasma adrenocorticotropic hormone (ACTH) and beta-endorphin (beta-EP) concentrations were measured by radioimmunoassay in 122 newborns, born vaginally after spontaneous labor between the 38th and the 41st week of pregnancy. Blood samples were taken from umbilical cord in 10 newborns and from antecubital vein in the remaining 112 newborns, divided into 8 groups aged from 12 h to 7 days. The mean (+/- SE) ACTH concentrations in cord plasma were 81.87 +/- 10.16 pg/ml and decreased significantly (p less than 0.01) at the 24th h of life (49.09 +/- 6.93 pg/ml). Afterwards mean ACTH plasma concentrations fluctuated around the latter values. The mean (+/- SE) B-EP concentrations in cord plasma were 21.96 +/- 3.12 pmol/l and decreased significantly at the 24th h of life (13.43 +/- 2.08 pmol/l; p less than 0.01). From the 24th h to the 7th day the mean plasma concentrations of beta-EP were not significantly different. ACTH and beta-EP plasma levels were positively correlated (p less than 0.001) at delivery and during the first seven days of life.