Effect of myiasis and acute restraint stress on plasma levels of immunoreactive beta-endorphin, adrenocorticotrophin (ACTH) and cortisol in the sheep

Cutaneous myiasis in sheep arising from the activity of Lucilia cuprina larvae can result in significant physiological changes in susceptible animals. The stress imposed on the pituitary-adrenal axis of the sheep in response to myiasis and acute restraint is the subject of this investigation. Merino wethers were exposed to handling restraint, and blood sampling, during examination for blowfly strike; where necessary, they were treated for cutaneous myiasis. Significant changes in the plasma concentrations of immunoreactive beta-endorphin (beta-EP), ACTH and cortisol were found in sheep with extensive myiasis, as compared with unstruck sheep or those with only localized myiasis. In five susceptible sheep with extensive cutaneous myiasis, mean plasma levels of beta-EP, ACTH and cortisol were 307 +/- 71 pg ml-1, 953 +/- 58 pg ml-1 and 232 +/- 46 nmol l-1 respectively, compared with 818 +/- 89 pg ml-1, 641 +/- 41 pg ml-1 and 107 +/- 17 nmol l-1 in six unstruck sheep handled similarly. Whereas significant increases in plasma ACTH and cortisol can result from pituitary-adrenal responses to acute emotional or surgical stress, and are usually accompanied by a concomitant release of beta-EP from the pituitary, the present findings indicate a marked reduction in beta-EP levels and a significant increase in ACTH and cortisol in sheep following blowfly strike and acute handling restraint. This result suggests that cutaneous myiasis in susceptible sheep can alter the pituitary-adrenal response to acute restraint stress, and this could occur either by an alteration of precursor processing in the pituitary or by the selective release of ACTH.     

Plasma beta-endorphin in response to oral glucose tolerance test in obese patients

In order to clarify the possible interaction between endogenous opioids and glucose homeostasis in obesity we studied Beta-Endorphin (B-Ep), ACTH, cortisol and insulin plasma levels in response to an oral glucose tolerance test (OGTT) in 8 females suffering from uncomplicated obesity and in 6 healthy volunteers of normal weight. Results were evaluated in terms of secretion areas subtracted from basal value. Basal glucose, insulin and B-Ep levels were significantly higher in the obese patients compared to controls, cortisol levels and ACTH were not statistically different between obese and normal subjects. During OGTT total areas of insulin secretion were significantly higher in the obese patients; cortisol, ACTH, B-Ep plasma levels did not change in controls, whereas obese patients showed a response to B-Ep which reached a peak at 60 minutes. The area of B-Ep response to OGTT in obese patients was significantly higher than in controls. On the basis of these results we may suggest that the opioid system belongs to the chain of neuroendocrine and metabolic events responsible for the origin and the growth of overweight. But the possibility exists that obesity itself can enhance the B-Ep secretion above all through overeating. In this regard it is to stress that glucose ingestion induces in obese patients, differently from normal subjects, insulin hypersecretion and the B-Ep secretion, possibly from gastro-enteric tract and/or pancreatic isles.     

Effects of acute acidemia on the fetal cardiovascular defense to acute hypoxemia

In complicated pregnancy, fetal hypoxemia rarely occurs in isolation but is often accompanied by fetal acidemia. There is growing clinical concern about the combined effects of fetal hypoxemia and fetal acidemia on neonatal outcome. However, the effects on the fetal defense responses to acute hypoxemia during fetal acidemia are not well understood. This study tested the hypothesis that fetal acidemia affects the fetal defense responses to acute hypoxemia. The hypothesis was tested by investigating, in the late-gestation sheep fetus surgically prepared for long-term recording, the in vivo effects of acute fetal acidemia on 1) the fetal cardiovascular responses to acute hypoxemia and 2) the neural and endocrine mechanisms mediating these responses. Under general anesthesia, five sheep fetuses at 0.8 gestation were instrumented with catheters and Transonic flow probes around the femoral and umbilical arteries. After 5 days, animals were subjected to an acute hypoxemia protocol during intravenous infusion of saline or treatment with acidified saline. Treatment with acidified saline reduced fetal basal pH from 7.35 +/- 0.01 to 7.29 +/- 0.01 but did not alter basal cardiovascular variables, blood glucose, or plasma concentrations of catecholamines, ACTH, and cortisol. During hypoxemia, treatment with acidified saline increased the magnitude of the fetal bradycardia and femoral vasoconstriction and concomitantly increased chemoreflex function and enhanced the increments in plasma concentrations of catecholamines, ACTH, and cortisol. Acidemia also reversed the increase in umbilical vascular conductance during hypoxemia to vasoconstriction. In conclusion, the data support our hypothesis and show that acute acidemia markedly alters fetal hemodynamic, metabolic, and endocrine responses to acute hypoxemia.     

Effect of stress-like concentrations of cortisol on the feedback potency of oestradiol in orchidectomized sheep

The effect of stress-like concentrations of cortisol on oestradiol-induced change in LH secretion and GnRH receptor expression was evaluated in orchidectomized sheep (wethers). Twenty-four wethers were assigned at random to one of the four treatment groups in a 2x2 factorial design (n=6 wethers/group). Wethers received cortisol (90 microg/kg/h; groups 2 and 4) or a comparable volume of cortisol delivery vehicle (groups 1 and 3) by continuous infusion for 48 h. During the final 24 h of infusion, wethers received oestradiol (6 ng/kg/h; groups 3 and 4) or oestradiol delivery vehicle (groups 1 and 2). The pattern of LH secretion was assessed during a 3-h period of intensive blood collection beginning 21 h after initiation of oestradiol infusion. Although neither cortisol nor oestradiol alone affected (P>0.05) mean serum concentration of LH or LH pulse frequency, serum LH and the frequency of secretory episodes of LH were significantly reduced (P<0.05) in wethers receiving cortisol and oestradiol in combination. Anterior pituitary tissue was collected at the end of the infusion period. Oestradiol increased (P<0.05) tissue concentrations of GnRH receptor and GnRH receptor mRNA. Although cortisol alone did not affect (P>0.05) basal concentrations of receptor or receptor mRNA, the magnitude of oestradiol-induced increase in GnRH receptor and GnRH receptor mRNA was significantly reduced in wethers receiving cortisol and oestradiol concurrently. Conversely, steady-state concentrations of mRNA encoding the LHbeta and FSHbeta subunits were increased (P<0.05) in wethers receiving cortisol. These observations demonstrate that stress-like concentrations of cortisol act in concert with oestradiol to suppress LH secretion. In addition, cortisol blocks oestradiol-dependent increase in pituitary tissue concentrations of GnRH receptor and GnRH receptor mRNA.     

Altered response to neuroendocrine challenge linked to indices of the metabolic syndrome in healthy adults

Metabolic syndrome (MetS) is characterized by central obesity, hypertension, insulin resistance, and hypercholesterolemia. Hypothalamic-pituitary-adrenal (HPA) axis activity is frequently abnormal in MetS, and excessive cortisol exposure may be implicated in metabolic derangements. We investigated the hypothesis that cortisol and adrenocorticotropic hormone (ACTH) responses to a standardized neuroendocrine challenge test would be associated with indices of MetS in a community sample of healthy adults. Healthy adults, 125 men and 170 women, without significant medical problems or chronic medications were recruited from the community. Participants completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test, and anthropometric measurements, blood pressure, glycosylated hemoglobin (HbA1c), and cholesterol were measured. Participants reported on their history of early life stress and recent stress, as well as mood and anxiety symptoms. Cortisol and ACTH responses to the Dex/CRH test were negatively associated with measures of central adiposity (p<0.001) and blood pressure (p<0.01), and positively associated with HDL cholesterol (p<0.01). These findings remained significant after controlling for body mass index (BMI). Measures of stress and anxiety and depressive symptoms were negatively correlated with cortisol and ACTH responses in the Dex/CRH test but were not related to MetS indices. That altered HPA axis function is linked to MetS components even in a healthy community sample suggests that these processes may be involved in the pathogenesis of MetS. Identification of premorbid risk processes might allow for detection and intervention prior to the development of disease.     

Cortisol inhibits ACTH but not the AVP response to hypoxaemia in fetal lambs at days 123-128 of gestation

During acute hypoxemia in fetal sheep the elevation in ACTH concentration in the fetal circulation at days 125-129 is greater than that at term, but similar rises in AVP occur at both times. To examine whether the diminished ACTH response is due to elevated endogenous cortisol, and if there is differential control of ACTH and AVP release in hypoxemia, we infused either vehicle or cortisol (5 micrograms/min) into fetal sheep at days 123-128 for 5 h before and then during a 2-h period of acute hypoxemia (mean PaO2 decrease 8.2 mmHg) without acidemia. During cortisol infusion, plasma cortisol rose to 40-50 ng/ml, similar to values in term fetuses. In vehicle-infused fetuses, cortisol rose from 2.1 to 7.0 ng/ml at +1 to +2 h of hypoxemia. ACTH rose significantly during hypoxemia in the vehicle-infused fetuses, and this response was attenuated by cortisol infusion. In contrast, fetal AVP rose significantly during hypoxemia both in the presence and absence of cortisol infusion. Fetal breathing movements, and electroocular activity decreased during hypoxemia, and these responses were not altered by cortisol. We conclude that cortisol exerts differential negative feedback on ACTH but not on AVP release during hypoxemia. The maintained AVP response may facilitate cardiovascular adjustments of the fetus to hypoxemia even when endogenous cortisol is elevated, such as near term.     

Effects of twinning, birth size, and postnatal growth on glucose tolerance and hypothalamic-pituitary-adrenal function in postpubertal sheep

Low birth weight is associated with postnatal physiological changes, including impaired glucose tolerance and increased cortisol secretion, that may predispose to disease in adulthood. Twins are born lighter than singletons, but there are conflicting data regarding the association between birth weight and postnatal physiology in twins. We studied glucose tolerance and ACTH and cortisol responses to a combined corticotropin-releasing hormone and arginine vasopressin (CRH + AVP) challenge in postpubertal female twin (n = 7 twin pairs) and singleton (n = 13) sheep from the same flock. There were no differences in glucose tolerance between twins and singletons and no association with birth weight. Twins had a greater ACTH (P < 0.05), but not cortisol, response to CRH + AVP than singletons. ACTH area under the curve was inversely related to birth weight in both singletons [R(2) = 0.31, P = 0.05; -8,311 (SD 3,736) pg.min.ml(-1).kg(-1)] and twins (R(2) = 0.49); in twins, this was due to the within-twin pair rather than the between-twin pair coefficient in the regression analysis [P = 0.02, -26,856 (9,806) vs. P = 0.1, 8,619 (4,950) pg.min.ml(-1).kg(-1)]. We conclude that the reduced fetal growth in twins has postnatal consequences for hypothalamic-pituitary-adrenal function and that this is determined by factors specific to the fetus (within-twin pair) rather than by shared maternal factors (between-twin pair). Studies investigating the associations between fetal growth and postnatal outcomes in twins benefit from an appropriate singleton control group and from analyses evaluating the contribution from both between- and within-pair coefficients in twins.     

Development of young rats and rabbits exposed to a strong electric field

Body growth and circulating levels of hormones were assessed in young rats and rabbits exposed to a 50-Hz electric field of 50 kV/m. Eight-week-old male rats were exposed 8 h/day for 4 weeks and rabbits were exposed 16 h/day from the last 2 weeks of gestation to 6 weeks after birth. The body and the organ growth of exposed rats were not statistically different from those of sham-exposed controls. No important differences from controls were observed in plasma levels of corticosterone, TSH, ACTH, and T4 or in adrenal levels of epinephrine, norepinephrine, and corticosterone although T3 was slightly, but significantly, decreased. No large histological changes in the thyroid or adrenals were noted. In rabbits, organ and body weights of exposed animals were comparable to those of controls. Plasma levels of various hormones (ACTH, GH, T3, T4, corticosterone, cortisol), serum glucose, triglycerides, and cholesterol were not significantly altered. Adrenal content of cortisol was lower, however, in exposed rabbits. No histological changes of the thyroid or adrenal glands were observed.     

Modulation of the responses of fetal sheep to adrenergic stimulation by adrenal demedullation and chemical sympathectomy

The responses to sympathetic stimulation of fetal sheep adrenal-demedullated or sympathectomised by infusion of guanethidine sulphate have been studied. Sympathetic responses in such denervated or sympathectomised fetuses was studied by intravenous infusion of adrenaline or noradrenaline at about 0.4 micrograms/min per kg. This infusion increased plasma concentration 100-200 fold and there was no significant difference between the control fetuses and those in the vasrious treatment groups. Catecholamine infusions at these rates normally have little effect upon fetal blood gas and pH values, but in adrenal-demedullated fetuses adrenaline infusion drepressed fetal arterial PO2 by 4-6 mmHg (P less than 0.05). The heart rate and blood pressure responses to catecholamine infusion in sympathectomised fetuses was, as expected, much increased. Similar observations were made on adrenal-demedullated fetuses, an unexpected finding, and this is taken to illustrate loss of the adrenal medulla is associated with enhanced responsiveness to adrenergic stimulation in peripheral tissues. The majority of the endocrine and metabolic responses, as reflected in fetal plasma concentrations of ACTH, cortisol, insulin, glucose, lactate and fatty acids, to catecholamine infusion were similarly much enhanced by adrenal-demedullation and chemical sympathectomy. Of particular note was a substantial increase in the responsiveness of the fetal adrenal, as reflected in plasma cortisol, to stimulation by ACTH, a change that usually induces labour, but not so in the present sheep. The results on increased sensitivity in adrenal-demedullated fetuses are discussed in relation to likely tissue mechanisms mediating the changes.     

橘皮素对高强度运动诱发的人体皮质醇应激反应的影响*

目的: 探讨4周橘皮素补充对高强度抗阻运动诱发的皮质醇应激反应的影响。方法: 将24名短跑运动员进行配对,随机分为试验组和对照组。试验组每天补充橘皮素补剂(含橘皮素200 mg),对照组每天补充安慰剂,为期4周。两组运动员均在干预前一日和干预后次日进行抗阻运动激发试验(推举、深蹲、卧推和硬拉,每个动作×4组×10RM)。采集受试者在运动激发试验前即刻(PRE)、试验后即刻(P0)以及第10(P10)、20(P20)和30(P30)分钟时的血液样本,测量血清皮质醇、促肾上腺皮质激素(ACTH)、超氧化物歧化酶(SOD)、白细胞计数(WBC)和血糖,以及PRE和P0时的血乳酸值。结果: 与干预前同期比较,补充橘皮素4周后,试验组在激发试验前PRE的血清皮质醇水平(P=0.017)、激发试验后P10的血清皮质醇水平(P=0.010)、激发试验后P20和激发试验后P30的血清皮质醇水平均显著降低(P＜0.05或 P＜0.01),试验组在激发试验前PRE的WBC、激发试验后P10的ACTH(P=0.037)和激发试验后P30的WBC、ACTH均显著降低(P＜0.05);与对照组比较,试验组在激发试验前PRE和激发试验后P10的血清皮质醇水平显著降低(P＜0.05),激发试验后P30的ACTH和WBC水平显著降低(P＜0.05,P＜0.01)、SOD活性水平显著升高(P＜0.05)。结论: 橘皮素能有效缓解高强度运动诱发的人体皮质醇应激反应,抑制皮质醇过度分泌,提升人体抗氧化能力,加速体内炎症消除,促进身体机能恢复。     

Plasma 6beta-hydroxycortisol measurements for assessing altered hepatic drug metabolizing enzyme activity

To study the usefulness of 6beta-hydroxycortisol (6betaOHF) measurements for assessing hepatic drug metabolizing enzyme activity, plasma 6betaOHF and cortisol were measured in 22 patients with alcoholic liver disease after at least 2 weeks of alcohol abstinence, in 5 patients with severe Cushing's syndrome and in 12 healthy non-drinker subjects. Blood samples were drawn under resting conditions during midnight, in the morning at 0800 h, after a 1-mg overnight dexamethasone test and after ACTH administration. Plasma cortisol and 6betaOHF were determined with radioimmunoassay. In patients with alcoholic liver disease, the plasma cortisol levels at midnight and 0800 h, as well as after the administration of dexamethasone and ACTH were not different from corresponding values measured in non-drinker controls. In addition, these patients with alcoholic liver disease had similar plasma 6betaOHF levels at midnight, 0800 h and after dexamethasone administration as compared to corresponding values in controls. By contrast, ACTH administration in patients with alcoholic liver disease resulted in a significantly (p<0.05) larger increase of plasma 6betaOHF (from 106 +/- 22 to 1102 +/- 106 ng/dl, mean +/- SE) as compared to that found in controls (from 74 +/- 3 to 337 +/- 76 ng/dl). The markedly increased 6betaOHF response to ACTH administration in patients with alcoholic liver disease was similar to that measured in patients with severe Cushing's syndrome, in whom increased and non-suppressible plasma cortisol levels were accompanied by markedly elevated plasma 6betaOHF levels. These results indicate that alcohol abstinence in patients with alcoholic liver disease is associated with an exaggerated 6betaOHF response to ACTH and that this abnormality may prove to be a clinically useful parameter for a sensitive detection of altered drug metabolism present in these patients.     

Comparative physiological responses of stress in sheep selected for resistance or susceptibility to Haemonchus contortus in semi-arid tropical region during different seasons

The present study was conducted to assess the comparative physiological responses of stress in sheep selected for resistance or susceptibility to Haemonchus contortus in the semi-arid region during different seasons. A total of 20 adult Malpura sheep from resistant and susceptibility line were selected for study. The intensity of strongyle infection, blood biochemical and cortisol levels were estimated monthly basis while meteorological data were collected everyday throughout the year. The temperature-humidity index was the highest during dry-hot season. The faecal egg count increased significantly (p < 0.05) during June–August (rainfall season) in susceptible sheep as compared to resistant sheep. The plasma cortisol level increased significantly (p < 0.05) in both the groups during dry hot (March–May) season and it remained higher in the susceptible line till June–August. The total plasma protein reduced significantly during hot-humid with scantly rainfall (September–November) season as compared to other season in susceptible line. It is pertinent to conclude that though sheep remained in stress during dry hot (March–May) season, but effects of stress on the intensity of strongyle infection and blood biochemical were better tolerated by animals of resistant line during hot-humid season compared to susceptible line under semi-arid region.     

Maternal exposure to dexamethasone or cortisol in early pregnancy differentially alters insulin secretion and glucose homeostasis in adult male sheep offspring

An adverse intrauterine environment increases the risk of developing various adult-onset diseases, whose nature varies with the timing of exposure. Maternal undernutrition in humans can increase adiposity, and the risk of coronary heart disease and impaired glucose tolerance in adult life, which may be partly mediated by maternal or fetal endocrine stress responses. In sheep, dexamethasone in early pregnancy impairs cardiovascular function, but not glucose homeostasis in adult female offspring. However, male offspring are often more susceptible to early life "programming". Pregnant sheep were infused intravenously with saline (0.19 ml/h), dexamethasone (0.48 mg/h), or cortisol (5 mg/h), for 2 days from 26 to 28 days of gestation. In male offspring, size at birth and postnatal growth were measured, and glucose tolerance [intravenous glucose tolerance test (IVGTT)], insulin secretion, and insulin sensitivity of glucose, alpha-amino nitrogen, and free fatty acid metabolism were assessed at 4 yr of age. We show that cortisol, but not dexamethasone, treatment of mothers causes fasting hyperglycemia in adult male offspring. Maternal cortisol induced a second-phase hyperinsulinemia during IVGTT, whereas maternal dexamethasone induced a first-phase hyperinsulinemia. Dexamethasone improved glucose tolerance, while cortisol had no impact, and neither affected insulin sensitivity. This suggests that maternal glucocorticoid exposure in early pregnancy alters glucose homeostasis and induces hyperinsulinemia in adult male offspring, but in a glucocorticoid-specific manner. These consequences of glucocorticoid exposure in early pregnancy may lead to pancreatic exhaustion and diabetes longer term and are consistent with stress during early pregnancy contributing to such outcomes in humans.     

Sex differences in cortisol secretion after administration of an ACTH analogue in sheep during the breeding and non-breeding season

The aim of this study was to compare the response of cortisol in sheep of different sex and gonadal status to adrenal cortex stimulation by an ACTH analogue in the breeding and non-breeding season. Twenty-four adult Corriedale sheep were used in the non-breeding season, and 19 in the breeding season. Three weeks prior to the first trial (non-breeding season), six rams and six ewes were gonadectomised. In each trial, blood was obtained every 15min for 9h and the animals received 0.5mg of ACTH (Tetracosactid, Synacthen Depot i.m., after 1.5h of sampling. Sampling began at 10:00a.m. in the non-breeding season and at 9:00a.m. in the breeding season. Three main effects (sex, gonadal status and season) were evaluated, each with two levels (male and female, intact and gonadectomised, breeding and non-breeding season, respectively). In both seasons, the females showed higher cortisol levels after ACTH than males (P<0.001), though the difference seemed less marked in the non-breeding season. The cortisol response in the ewes was not affected by season. The rams, however, showed a lower response in the breeding season (P<0.03). Gonadectomy reduced the response in the ewes (P<0.001) but had no effect in the rams. Nevertheless, gonadectomy also eliminated the differences between the ewes and the rams, such that the intact rams had lower levels of cortisol compared to the intact females, with those of the gonadectomised animals of both sexes being intermediate between the gonad-intact groups. The results of this study confirm sex differences in ACTH induced cortisol secretion in intact sheep in vivo. Furthermore, by applying exogenous ACTH we have directly stimulated the adrenal cortex, indicating the existence of sex differences also at this level. The circulating gonadal steroids, which are responsible at least in part for the sex differences in the responses to stress, may influence cortisol secretion from the adrenal gland by direct action at the cortex.     

ACTH,cortisol and glucose responses after administration of vasopressin in cattle and sheep

The present study compared the effects of vasopressin on plasma concentrations of corticotropin, cortisol and glucose in cattle and sheep. After intravenous injection of 1, 0.1 and 0.01 g vasopressin per kg body weight, the plasma vasopressin concentration increased proportionally to the injected dose, and this increase was similar in cattle and sheep. Doses of 1 and 0.1 g per kg body weight of vasopressin triggered significant responses of corticotropin, cortisol and glucose in cattle and sheep. The corticotropin response to both doses was significantly greater in sheep, whereas the glucose response was greater in cattle. The cortisol response did not differ between species. The lowest dose of vasopressin (0.01 g per kg body weight) still induced a significant cortisol response without a substantial effect on plasma corticotropin, suggesting that a direct action of vasopressin on the adrenals may contribute to the observed cortisol response. The results demonstrate that vasopressin increases plasma levels of corticotropin, cortisol and glucose in cattle, as it does in sheep, but the intensities of the corticotropin and glucose responses to vasopressin differ between cattle and sheep. The reasons for these differences remain to be clarified.Abbreviations ACTH corticotropin - AVP vasopressin - bw body weight     

ADRENAL FUNCTION IN WILD AND REHABILITATED PACIFIC HARBOR SEALS (PHOCA VITULINA RICHARDII) AND IN SEALS WITH PHOCINE HERPESVIRUS-ASSOCIATED ADRENAL NECROSIS

Adrenal function in harbor seals (Phoca vitulina richardii) was evaluated using adrenocorticotrophic hormone (ACTH) stimulation tests and fecal cortisol levels. The effect of ACTH administration on plasma cortisol and aldosterone levels in five free-living and 14 rehabilitated harbor seal pups was determined using enzyme immunoassay and radioimmunoassay, respectively. In free-living seals, injection of ACTH caused a significant increase in mean plasma cortisol but not of mean aldosterone levels 60 min postinjection. In these seals, mean initial plasma aldosterone was significantly higher than initial levels in rehabilitated seals, while initial cortisol levels were similar. Of the rehabilitated seals, eight died with adrenal cortical necrosis associated with herpesvirus inclusions, while six lived to be released. In the seals that were released, both mean initial cortisol levels and response to ACTH decreased through rehabilitation. In the seals that died, mean initial cortisol and response to ACTH increased through rehabilitation. The differences between initial cortisol levels in seals that lived and those that died were significant at weeks two and four of rehabilitation but not at the week of admission. There was considerable individual variation in initial plasma aldosterone levels and responses to ACTH, although initial aldosterone levels were significantly higher in rehabilitated seals that died than in seals that lived. Seals with adrenal necrosis associated with herpesvirus infection did not have decreased adrenal hormone responses to ACTH. Differences between initial hormone levels and responses to ACTH in different groups of seals may be associated with differing stress levels. Fecal cortisol assays were not a useful method of assessing adrenal function in these seals, as measured levels did not correlate with plasma cortisol levels.     

The effects of metabolic stress on plasma progesterone in healthy volunteers and schizophrenic patients.

A number of preclinical studies suggest that progesterone may play an important role in the stress response, however, the effects of stress on progesterone in humans has not been established. Also, several lines of evidence indicate that schizophrenia may be associated with abnormal neurobiological responses to stress, but the effects of stress on progesterone in schizophrenia has not been investigated. The purpose of the present study was to examine the effects of stress on plasma progesterone and cortisol in healthy subjects and to determine if schizophrenic patients have altered stress-induced plasma progesterone levels compared to normal controls. Stress was induced through administration of 2-deoxyglucose (2DG), a glucose analog that impairs glucose metabolism resulting in a clinical state comparable to hypoglycemia. There were significant increases in plasma progesterone and cortisol levels following 2DG-induced glucoprivic stress in healthy controls. There was no relationship between stress related progesterone and cortisol elevations. Schizophrenic patients, in comparison to controls, had significantly greater 2DG-induced elevations in progesterone levels but no differences in stress-related cortisol levels. There was evidence that basal progesterone and cortisol levels were elevated in the schizophrenic patients. The implications of these data are discussed.     

橘皮素与乳清蛋白的合用对短跑运动员冬训期间血清睾酮、皮质醇水平的影响*

目的:探讨补充橘皮素对短跑运动员冬训期间血清睾酮、皮质醇水平的影响。方法:将24名短跑运动员配对、随机分为试验组和对照组。冬训期间,试验组补充橘皮素补剂(含橘皮素200 mg),对照组补充安慰剂,为期4周。分别在每周第一天(T1、T2、T3、T4)及干预结束次日(T5)采集血液样本,检测血清睾酮、皮质醇、超氧化物歧化酶(SOD)、促肾上腺皮质激素(ACTH)等指标,并在干预开始和结束时测试身体成分。结果:干预4周后,①对照组的血清皮质醇水平上升,血清睾酮和SOD活性水平显著下降(P＜0.05);②试验组的血清皮质醇(P＜0.05)和ACTH(P＜0.01)均显著下降,血清睾酮维持稳定,SOD活性水平小幅上升;③试验组和对照组的肌肉量均有增加,但前者的增加量显著大于后者。结论:补充4周橘皮素能减少冬训期间高强度运动引起的机体氧化应激反应,维持机体血清睾酮水平稳定,抑制皮质醇过度分泌,促进肌肉合成。     

Elevated Hair Cortisol Levels among Heroin Addicts on Current Methadone Maintenance Compared to Controls

Whether methadone maintenance treatment (MMT) can improve the basal function of the hypothalamic–pituitary–adrenal (HPA) axis, which is suppressed by long-term heroin consumption, is a matter of debate. The stress state and depression and anxiety symptoms may affect the basal activity of the HPA axis in MMT patients. However, the effect of psychological factors on HPA activity was not simultaneously controlled in previous studies. This study investigated differences in HPA basal activity between MMT patients and controls using psychological variables as covariates. The participants included 52 MMT patients and 41 age-matched, non-heroin-dependent controls. Psychological states were self-reported with the Perceived Stress Scale, Self-Rating Depression Scale and Self-Rating Anxiety Scale. The hair cortisol level was adopted as a biomarker of HPA basal activity and was determined with liquid chromatography tandem mass spectrometry. The results revealed that MMT patients had significantly higher hair cortisol levels than the controls (p<0.05), but the difference was not significant (p>0.05) when the perceived stress, depression and anxiety scores were used as covariates. We concluded that patients with long-term MMT showed higher basal activity of the HPA axis. The high chronic stress state and increase in depression and anxiety symptoms may mask the suppression effect of methadone on the HPA activity.     

Ovine fetal adrenal maturation at term and during fetal ACTH administration: evidence that the modulating effect of cortisol may involve cAMP

Exogenous ACTH1-24 promotes adrenal maturation in fetal sheep, and this effect appears to be modulated in part by cortisol (Challis et al. 1985). We have examined whether similar changes in adrenal metabolism of progesterone occur with ACTH-induced labour as at spontaneous term and whether the site of cortisol modulation is on adrenal steroidogenesis or at the level of cAMP generation. Chronically catheterized fetal sheep were infused in utero for 100 h between days 127 and 131 of pregnancy with P-ACTH, P-ACTH + metopirone, P-ACTH + metopirone + cortisol, or saline. After 100 h the metabolism of [3H]progesterone was measured in adrenal homogenates. Similar incubations were performed with adrenal tissue from fetal sheep at day 130 of pregnancy and at spontaneous labour. In the treatment groups of sheep, cAMP output by dispersed adrenal cells in response to ACTH added in vitro was also determined. Similar qualitative patterns of [3H]progesterone metabolism were found in adrenal homogenates after in vivo ACTH or at term. At both times there was an increase in cortisol and in total 17 alpha-hydroxycorticosteroid accumulation and also evidence for increased activity of 11 beta-hydroxylase enzyme. The formation of total 17 alpha-hydroxycorticosteroids was not affected significantly by concurrent treatment in vivo with metopirone +/- cortisol. The accumulation of cAMP in vitro was increased after in vivo ACTH, attenuated after ACTH + metopirone, but statistical significance over controls was restored after ACTH + metopirone + cortisol treatment. We conclude that ACTH-induced labour and spontaneous parturition in sheep is associated with qualitatively similar changes in progesterone metabolism by the fetal adrenal gland.(ABSTRACT TRUNCATED AT 250 WORDS)