Plasma Β-endorphin Concentrations Research Articles

Differences in the Peripheral Levels of ??-endorphin in Response to Alcohol and Stress as a Function of Alcohol Dependence and Family History of Alcoholism

Evidence indicates that both genetic and environmental factors, such as stress, may play an important role for the development of alcoholism, while beta-endorphin may be implicated in the control of alcohol consumption. The objective of the present studies was to test the hypothesis that there are differences in the response of the pituitary beta-endorphin system to stress as a function of family history of alcoholism and alcohol dependence. The response of the pituitary beta-endorphin to a placebo or an alcohol (0.50 g ethanol/kg) drink and to a stress task performed 30 min following ingestion of either the placebo or the alcohol drink was measured in social and heavy drinkers with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism. Thus, each subject participated in 4 experimental sessions given on different days in a randomized order. Four groups of subjects were investigated: 1) low risk nonalcoholics (LRNA); 2) high risk nonalcoholics (HRNA), 3) low risk alcoholics (LRA); and 4) high risk alcoholics (HRA). Plasma beta-endorphin was estimated prior to and for 3.5 hr post-stress. Changes in the concentration of plasma beta-endorphin following ingestion of either the placebo or alcohol drink without performance of the stress task served as controls to compare the stress-induced changes. Basal plasma beta-endorphin levels were higher in LRNA than LRA, HRNA and HRA participants, while basal plasma beta-endorphin levels were higher in LRA than those in HRNA and HRA participants. Furthermore, there was no significant difference in the plasma beta-endorphin levels between HRNA and HRA participants. Stress, induced a significant increase in plasma beta-endorphin concentration in all four groups of participants. However, the stress-induced increase in plasma beta-endorphin levels was more pronounced in LRNA than HRNA, LRA and HRA participants. Thus, alcohol dependence decreased the basal plasma beta-endorphin levels in LR only, as well as the stress induced increase in plasma beta-endorphin levels of participants without, but not of those with, a family history of alcoholism. Alcohol prior to stress attenuated the stress-induced increase in plasma beta-endorphin levels of all four groups of participants. The present data indicates that there are differences in both, the basal plasma beta-endorphin levels as well as the response of the pituitary beta-endorphin to stress as a function of family history of alcoholism and alcohol dependence. Thus, in HR individuals a dysfunction in the activity of the pituitary beta-endorphin system predates the development of alcoholism, while in LR individuals it develops following alcohol dependence. Furthermore, alcohol dependence did not alter the alcohol-induced attenuation of beta-endorphin response to stress.

The effect of active immunization against adrenocorticotropic hormone on cortisol, β-endorphin, vocalization, and growth in pigs1

Because the poor growth performance of intensively housed pigs is associated with increased circulating glucocorticoid concentrations, we investigated the effects of glucocorticoid suppression by inducing a humoral immune response to ACTH on physiological and production variables in growing pigs. Grower pigs (28.6 +/- 0.9 kg) were immunized with amino acids 1 through 24 of ACTH conjugated to ovalbumin and suspended in diethylaminoethyl (DEAE) dextran-adjuvant or adjuvant alone (control) on d 1, 28, and 56. The ACTH-specific antibody titers generated suppressed increases in cortisol concentrations on d 63 in response to an acute stressor (P = 0.002; control = 71 +/- 8.2 ng/mL; ACTH-immune = 43 +/- 4.9 ng/mL) without altering basal concentrations. Plasma beta-endorphin concentrations were also increased (P < 0.001) on d 63 (control = 18 +/- 2.1 ng/mL; ACTH-immune = 63 +/- 7.3 ng/mL), presumably because of a release from negative feedback on the expression of proopiomelanocortin in pituitary corticotropes. Immunization against ACTH did not alter ADG (P = 0.120; control = 1,077 +/- 25; ACTH-immune = 1,143 +/- 25 g) or ADFI (P = 0.64; control = 2,719 +/- 42; ACTH-immune = 2,749 +/- 42 g) and did not modify behavior (P = 0.681) assessed by measuring vocalization in response to acute restraint. In summary, suppression of stress-induced cortisol responses through ACTH immunization increased beta-endorphin concentrations, but it did not modify ADG, ADFI, or restraint vocalization score in growing pigs.

Chronobiology and anesthesia.

CHRONOBIOLOGY investigates biologic rhythms that are involved in the organization of living organisms. Biologic rhythms consist of variations of biologic phenomena that are periodic and foreseeable in time. They are genetically determined as indicated by their persistence during constant conditions such as continuous light or darkness. Temporal variations in cycles of light– dark, rest–activity, fasting–eating, and other environmental conditions, defined as synchronizers, give the organism temporal markers and thus impose their period on these biologic rhythms. These rhythms can therefore be characterized by different periods, leading to the division of circadian (a period of approximately 24 h), ultradian (a cycle that is shorter than 1 day), and infradian (a cycle that may last weeks, months, or seasons). These clocks influence how our bodies change throughout the day, affecting blood pressure, activity of the immune system, blood coagulation, and gastric and renal functions. Almost all hormones are regulated by circadian rhythms. For example, cortisol naturally decreases to its lowest concentrations at bedtime and reaches its highest concentrations during the early waking hours. This variation may be fit to a sinusoidal function by the cosinor method, a linear method of least squares (fig. 1). This function is characterized by parameters such as the midline-estimating statistic of rhythm (MESOR), i.e., the mean level that is equal to the 24-h average), amplitude (half of the peak-to-trough difference of the fitted cosinus function), and acrophase (the crest time of rhythm given in degrees, where 360° corresponds to a 24-h cycle, or in hours and minutes). Other methods, such as Fourier transformation, may be used to detect the periodicity of the rhythm. Biologic rhythms are influenced by socioecologic factors, such as jet lag and shiftwork, as well as by illness and drugs. Available clinical data have shown that signs and symptoms are not constant over time and often have cyclic patterns. More strokes and heart attacks occur in the morning compared with any other time of day, and people with osteoarthritis tend to feel less pain in the morning than at night. Studies also suggest that chemotherapy and treatments for asthma and arthritis may be more effective and less toxic if drugs are administered at carefully selected times. Taking into account the circadian rhythms for medical treatment by choosing the time of day for drug administration is called chronotherapy. Drug effects can be optimized and side effects can be reduced by basing drug administration on the circadian patterns of a disease. Chronopharmacology is the study of the influence of the moment of administration of a drug (hour, month, and year) on its response according to the temporal structure of the organism receiving it. Chronopharmacology also studies the drug-induced alterations of biologic rhythms. Two aspects of chronopharmacology must be distinguished: the time of administration of a drug may determine a different response from a qualitative or a quantitative point of view (chronopharmacodynamics) and/or a different effective drug concentration (chronopharmacokinetics). Pharmacokinetic parameters are influenced by different physiologic functions displaying circadian rhythm. Temporal changes of drug kinetics have been reported in animals and humans for more than a hundred drugs, including anesthetics. It has been shown, for example, that despite a constant infusion rate of heparin, the risk of bleeding and the activated partial thromboplastin are higher at night. Chronopharmacokinetic data may partly explain chronopharmacodynamic phenomena. Knowledge of the influence of the time of administration on the drug kinetics could therefore have implications for its prescription by modulating the distribution of the total daily dose over a 24-h period. The aim of this review is to provide an update on the chronobiologic and chronopharmacologic findings that could have an impact on the daily practice of anesthesiology and/or research in this area.

Effects of Cool and Hot Humid Environmental Conditions on Neuroendocrine Responses of Horses to Treadmill Exercise

To determine the effects of exercise, high heat and humidity and acclimation on plasma adrenaline, noradrenaline, β-endorphin and cortisol concentrations, five horses performed a competition exercise test (CET; designed to simulate the speed and endurance test of a three-day event) in cool dry (CD) (20°C/40% RH) and hot humid (30°C/80% RH) conditions before (pre-acclimation) and after (post-acclimation) a 15 day period of humid heat acclimation. Plasma adrenaline and noradrenaline concentrations pre-acclimation were significantly increased compared with exercise in the CD trial at the end of Phases C ( P<0.05) and D ( P<0.05 and P<0.01, respectively) and at 2 min recovery ( P<0.01), with adrenaline concentrations still elevated after 5 min of recovery ( P<0.001). Plasma β-endorphin concentrations were increased at the end of Phases C ( P<0.05) and X ( P<0.01) and at 5 and 30 min recovery ( P<0.05) in the pre-acclimation session. Plasma cortisol concentrations were elevated after the initial warm up period pre-acclimation ( P<0.01) and at the end of Phase C ( P<0.05), compared with the CD trial. A 15 day period of acclimation significantly increased plasma adrenaline concentrations at 2 min recovery ( P<0.001) and plasma cortisol concentration at the end of Phase B ( P<0.01) compared with pre-acclimation. Acclimation did not significantly influence noradrenaline or β-endorphin responses to exercise, although there was a trend for plasma β-endorphin to be lower at the end of Phases C and X and after 30 min recovery compared with pre-acclimation. Plasma adrenaline, noradrenaline, β-endorphin and cortisol concentrations were increased by exercise in cool dry conditions and were further increased by the same exercise in hot humid conditions. Exercise responses post-acclimation suggest that adrenaline and noradrenaline may play a role in the adaptation of horses to thermal stress and that changes in plasma β-endorphin concentrations could be used as a sensitive indicator of thermal tolerance before and after acclimation. The use of plasma cortisol as a specific indicator of heat stress and thermal tolerance before or after acclimation in exercising horses appears limited.

Group differences in pain modulation: pain-free women compared to pain-free men and to women with TMD

Previously reported differences in sensitivity to experimental pain stimuli between the sexes, as well as between temporomandibular disorder (TMD) patients and healthy control subjects, may be attributable in part to group differences in two pain modulatory mechanisms: the baroreceptor reflex arc and the endogenous opioid system. Twenty-two pain-free (PF) men, 20 PF women and 20 women with TMD underwent two testing sessions in which heat pain and ischemic arm pain threshold and tolerance were measured during both sessions, but followed relaxation during one session and laboratory stress tasks during the other. Blood pressure (BP) and plasma β-endorphin (βE) concentration were measured during a baseline rest and during the stress or relaxation periods. PF men's threshold and tolerance for heat pain, but not for ischemic pain, exceeded that of PF women's during both sessions. PF women and TMD women did not differ in sensitivity to either pain modality; however, significantly lower ischemic pain threshold (IPTh) was linked to oral contraceptive use in PF women but not TMD patients. In the men alone, higher baseline systolic BP (SBP) was correlated with higher heat pain threshold on both days and heat pain tolerance on the stress day. Conversely, in TMD women, higher baseline SBP was correlated with lower ischemic pain tolerance (IPTol) on both days; BP and pain sensitivity were not related in PF women. In men, but not in PF or TMD women, stress systolic and diastolic BP were positively correlated with heat pain threshold and tolerance and higher diastolic reactivity to stress were correlated with higher heat pain and IPTh and tolerance. On the stress day, higher baseline βE level was strongly associated with higher IPTol in PF women but marginally associated with lower IPTol in TMD women. Thus, it appears that a BP-related analgesic mechanism (probably baroreceptor-mediated) predominates in PF men, while an endogenous opioid mechanism predominates in PF women. Stress enhances the expression of these central mechanisms. Female TMDs appear unable to effectively engage normal pain-inhibitory systems; opioid receptor desensitization and/or downregulation are probably implicated, because TMDs' production of βE appears normal.

Plasma β-endorphin levels in obese and non-obese patients with polycystic ovary disease

The aim of this study was to determine the influence of body weight on circulating plasma levels of β-endorphin and insulin in women with polycystic ovary disease (PCOD) ,as well as the correlation between the plasma levels of β-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited ,117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of β-endorphin ,insulin ,gonadotropins ,prolactin ,progesterone ,17β-estradiol ,estrone ,androgens ,dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean β-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and β-endorphin ,β-endorphin and BMI (and weight) ,insulin and BMI (and weight) ,and a negative correlation was found between insulin and SHBG. A weak association was found between-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma-endorphin concentrations correlate more with BMI than with insulinemia.

Plasma β-endorphin levels in obese and non-obese patients with polycystic ovary disease

The aim of this study was to determine the influence of body weight on circulating plasma levels of β-endorphin and insulin in women with polycystic ovary disease (PCOD) ,as well as the correlationbetween the plasma levels of β-endorphin and insulin.One-hundred and sixty-seven consecutive subjects with PCOD were recruited ,117 of whom had normal weight (body mass index (BMI) < 25) while50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of β-endorphin ,insulin ,gonadotropins ,prolactin ,progesterone ,17β-estradiol ,estrone ,androgens ,dehydroepiandrosteronesulfate and sex hormone-binding globulin (SHBG) were measured.Mean β-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones.Correlation analysis showed a positive association between insulin and β-endorphin ,β-endorphin and BMI (and weight) ,insulin and BMI (and weight) ,and a negative correlation was found betweeninsulin and SHBG. A weak association was found between-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma-endorphin concentrationscorrelate more with BMI than with insulinemia.

Effects of exercise intensity and duration on plasma beta-endorphin concentrations in horses.

To determine the relationship between plasma beta-endorphin (EN) concentrations and exercise intensity and duration in horses. 8 mares with a mean age of 6 years (range, 3 to 13 years) and mean body weight of 450 kg. Horses were exercised for 20 minutes at 60% of maximal oxygen consumption (VO2max) and to fatigue at 95% V02max. Plasma EN concentrations were determined before exercise, after a 10-minute warmup period, after 5, 10, 15, and 20 minutes at 60% VO2max or at the point of fatigue (95% VO2max), and at regular intervals after exercise. Glucose concentrations were determined at the same times EN concentrations were measured. Plasma lactate concentration was measured 5 minutes after exercise. Maximum EN values were recorded 0 to 45 minutes after horses completed each test. Significant time and intensity effects on EN concentrations were detected. Concentrations were significantly higher following exercise at 95% VO2max, compared with those after 20 minutes of exercise at 60% VO2max (605.2 +/- 140.6 vs 312.3 +/- 53.1 pg/ml). Plasma EN concentration was not related to lactate concentration and was significantly but weakly correlated with glucose concentration for exercise at both intensities (r = 0.21 and 0.30 for 60 and 95% VO2max, respectively). A critical exercise threshold exists for EN concentration in horses, which is 60% VO2max or less and is related to exercise intensity and duration. Even under conditions of controlled exercise there may be considerable differences in EN concentrations between horses. This makes the value of comparing horses on the basis of their EN concentration questionable.

The behavioural, physiological and immunological responses of lambs from two rearing systems and two genotypes to exposure to humans

The behavioural, physiological and immunological responses of lambs from two rearing systems and two genotypes to exposure to humans was assessed during and immediately after testing in an open-field arena. Ninety-six lambs of two genotypes (Scottish Blackface: BF and Texel×(Blue-faced Leicester×Scottish Blackface): T) were used. From birth to weaning one of two management regimes was applied: extensive (E), whereby animals were handled as little as possible or semi-intensive (I), in which lambs experienced a greater level of human exposure. Eight lambs from each of the four treatment groups received an antigenic challenge ( Mycobacterium a. paratuberculosis) at 9 weeks of age to allow subsequent testing of immunological reactivity. At 1 and 3 weeks after weaning and 1 year later, lambs were tested in groups of four in a 4.5×4.5 m indoor arena, marked with gridlines at 0.75 m intervals. There were a number of occasions where testing revealed significant effects of genotype, management or their interaction, but in an approximately equal number of instances no significant effects of either genotype or management were observed. Genotype significantly influenced the number of squares occupied in the test arena over a 10-min period before the human entered (100.4 vs. 110.5; sed 2.70 for BF and T lambs, respectively, p<0.001). In relation to the number of new squares entered, there was a genotype×management interaction: BFE lambs entered fewer squares than TE lambs but following semi-intensive management (I) BF lambs entered more squares than T lambs ( p<0.05). When a human entered the arena after this 10-min period, while there was a gradual reduction in the number of animals which had not moved over the next 5 min, 66 animals had not moved within the allocated time. Also during this period, BF lambs stood facing the human for significantly longer than T lambs ( p<0.05). At the time of arena testing, 12 lambs from each treatment group were fitted with heart-rate monitoring equipment. There were significant differences in heart rate in relation to period of testing, i.e. before (107.9) or after (112.3) the point at which the human entered the arena or when the lambs were walking in the presence of a moving human (126.3 b.p.m.; sed 2.15, p<0.001). When lambs were alone in the test arena, BF lambs had higher heart rates than T lambs ( p<0.05). The heart rate of E lambs increased more than that of I lambs when the human entered the pen (9.4 vs. 0.3 b.p.m.; sed 3.95, respectively; p=0.05). Immediately following completion of the behavioural tests, blood samples were collected from subsets of lambs. Plasma cortisol concentrations of BF lambs were greater than those of T lambs (82.0 vs. 53.5 nmol/l; sed 10.18, p<0.01) but there was no effect of management. Blood samples collected from the lambs challenged with a novel antigen prior to weaning showed a genotype but not a management effect on both antibody and cell mediated immune responses, although there was a genotype×management interaction. However, it should also be noted that there were no significant effects of either genotype or management on a number of the indices recorded: latency of lambs to move from the initial entry position in the absence or subsequent presence of a human; length of time one individual was separated from the other three; distance moved in a raceway before stopping; plasma β-endorphin concentrations; heart rate in the presence of a human. Overall, these results suggest that although differences in responsiveness associated with specific genotypes of sheep can be detected in a test situation, the early life management regime may also have an effect. The results of this study caution against drawing conclusions between studies where different genotypes are employed.

Plasma cortisol and beta-endorphin concentrations in trained and over-trained standardbred racehorses.

The effects of training and over-training on plasma cortisol and beta-endorphin (betaEP) concentrations at rest and after standardised exercise tests and the cortisol responses to adrenocorticotropin (ACTH) administration were investigated in standardbred horses. Twelve horses were divided randomly into control and over-trained (OT) groups after 17 weeks slow- and moderate-intensity treadmill training. The standardised treadmill exercise test consisted of 2 min at velocities corresponding to 30, 50, 70 and 100% of maximum O2 consumption. Over-training, defined as a significant decrease in body weight and treadmill run-time-to-fatigue in an incremental velocity test, occurred in the OT group after 32 weeks of training exercise. Peak cortisol concentrations after exercise decreased significantly in the OT group from 320+/-15.6 at week 8 to 245+/-17.0 nmol l(-1) at week 32, and mean cortisol concentrations over a 120-min period after exercise decreased from 258+/-11.7 to 192+/-16.6 nmol l(-1) (P<0.05). Mean and total cortisol and betaEP concentrations in resting horses were not significantly different after over-training. Peak cortisol concentrations after adrenocorticotropin (ACTH) administration were not significantly different in the over-trained group. Dysfunction of the hypothalamo-pituitary-adrenocortical axis occurs in over-trained horses, but this adaptation is not associated with a change in the adrenocortical responsiveness to ACTH.

Effects of age and maternal reactivity on the stress response of the pituitary-adrenocortical axis and the sympathetic nervous system in neonatal pigs

AbstractThe study was conducted to investigate the adreno cortical capacity after injection of ACTH and the sensitivity of the pituitary and the adrenal to immobilization in neonatal pigs at different ages. Furthermore, the endocrine reactivity of the offspring was compared with the stress reactivity of their mothers. Four piglets were selected from each of six different litters and subjected to an immobilization test and an adrenal function test using synthetic ACTH1-24 at the ages of 7, 21 and 35 days; the six sows were also subjected to restraint and an ACTH stimulation test. Plasma β-endorphin, norepinephrine and epinephrine concentrations were measured in blood samples taken 2 min after restraint and cortisol concentrations were measured 60 min after ACTH administration. A highly sensitive adrenal response was demonstrated in both sows and piglets and adrenal reactivity showed also a considerable consistency over time within sows. In neonatal pigs, the cortisol response to ACTH was greatest on day 7 and decreased up to day 35. Plasma epinephrine and norepinephrine levels after the 2-min immobilization were also higher at day 7 compared with the other ages (P &lt; 0·01). Piglets from sows, classified as high reacting according to their cortisol or epinephrine response, also showed significantly higher cortisol levels after ACTH challenge at all ages and significantly higher epinephrine levels after restraint at day 7 than piglets from low reacting sows. The results show an age-related change of pituitary-adrenocortical and sympatho-adrenomedullary responses in neonatal pigs and an absence of a stress hyporesponsive period at all ages studied. The results also indicate different levels of excitability in the offspring depending on the maternal stress reactivity.

Role of endogenous opioids in syncope induced by head-up tilt test and its relationship with isoproterenol-dependent and isoproterenol-independent neurally-mediated syncope

This study was designed to evaluate the role of endogenous opioids in neurally-mediated syncope. Head-up tilt test was performed on 35 patients with syncope of unknown origin. Plasma β-endorphin was measured (1) at baseline, (2) at the end of tilt test or at time of syncope, (3) 15 min before isoproterenol-test, (4) at the end of the isoproterenol-test or at time of syncope. Subjects with a positive tilt testing showed a larger rise in plasma β-endorphin concentrations at time of syncope (baseline 13.7±8.0 vs. syncope 41.4±26.4 pmol l −1; P<0.01). On the contrary, patients with a positive isoproterenol-test showed no rise in plasma β-endorphin levels (baseline 7.9±3.6 vs. syncope 7.4±2.7 pmol l −1; P=ns). Patients with a passive negative tilt test (baseline 6.7±2.8 vs. end of test 7.0±3.3 pmol l −1; P=ns) and negative isoproterenol tilt test (baseline 7.4±3.8 vs. end of test 8.1±3.4 pmol l −1; P=ns) showed no changes in β-endorphin concentrations. To further examine the efficacy of i.v. naloxone to prevent syncope, 10 patients were randomized to naloxone (0.02 mg/kg) or placebo. Second head-up tilt testing was negative in 1/5 patients with naloxone and in 2/5 patients with placebo. We conclude that, (1) endogenous opioids seem to be involved in vasovagal syncope induced by baseline head-up tilt test, (2) changes in plasma β-endorphin concentrations show significant differences between patients who have isoproterenol-dependent and isoproterenol-independent syncope, this finding might occur in the setting of different pathophysiologic mechanisms, and (3) intravenous naloxone at a dose of 0.02 mg/kg was not superior to placebo in order to prevent positive responses to baseline tilt test.

Effects of stress resulting from short-term restraint on in vitro functional capacity of leukocytes obtained from pigs

Abstract Objective To investigate whether the procedure used to snare and restrain pigs during collection of blood samples would alter in vitro functional capacity of leukocytes in the samples. Animals 8 gilts. Procedure Catheters were surgically inserted into the jugular vein of gilts to enable blood sample collection without restraint. After collection of a control sample, gilts were restrained by use of a snare and samples were collected at 0.5, 3.5, and 6.5 minutes after start of restraint (0 minutes). At each time point, plasma β-endorphin and cortisol concentrations as well as WBC counts were recorded, and functional capacity of leukocytes in cultures of whole blood was assessed by means of mitogen-induced proliferation and interleukin-2 activity, virus-induced interferon-α concentration, and phagocytosis of zymosan particles. Results Concentrations of plasma β-endorphin and cortisol were increased at 3.5 and 6.5 minutes after start of restraint. At these times, virus-induced interferon-α concentration was decreased, whereas proliferative response to Concanavalin A and phytohemagglutinin increased in samples collected at 6.5 minutes. Conclusion and Clinical Relevance It was possible to snare pigs for the purpose of collecting blood samples and restrain them without causing excessive stress that would affect immunologic variables, provided that the collection procedure was completed within a few minutes. (Am J Vet Res 1998;59:421–425)

The effect of environment on behavioural activity, ACTH, (β-endorphin and cortisol in pre-farrowing gilts

AbstractThis study examined the temporal relationships between behavioural activity and hormones associated with stress in gilts farrowing in two environments. Thirty-one Large White × Landrace gilts with indwelling jugular catheters were blood sampled daily (08.00 and 16.00 h) from 10 days before their expected parturition date (EPD). Five days before EPD they were moved to either a farrowing crate (C) with no bedding, or a pen (P) (2·5 m × 3·0 m) with straw provided and were blood sampled daily at 08.00, 12.00 and 16.00 h. Around 12 h before the onset of farrowing an extension was fitted to the catheter and blood samples were taken remotely at 30-min intervals. The posture of the gilts was recorded using 5-min scan samples over the 24 h pre-farrowing. The proportion of scans standing (an index of activity) was strongly affected by time (P &lt; 0·001) with peak levels at approximately 8 h pre-farrowing in both treatments, and by treatment (0·25 v. 0·33 (s.e.d. 0·03) for C and P gilts respectively; P &lt; 0·05). Plasma cortisol concentrations also increased before farrowing (P &lt; 0·001) reaching a peak at 12 to 6 h pre-farrowing. Crated gilts had higher cortisol concentrations than, penned gilts (overall mean 41·5 v. 30·7 (s.e.d. 3·8) [μg/l for C and P gilts respectively; P &lt; 0·05) at 24 to 12 (P &lt; 0·05), 12 to 6 (P &lt; 0·01) and 6 to 2 (P &lt; 0·05) h pre-farrowing. Plasma ACTH concentration showed a similar pattern to cortisol over the pre-parturient period, peaking at 12 h pre-farrowing in both treatments (time: P &lt; 0·001); crated gilts had significantly higher concentrations of ACTH at 6h pre-farrowing only (P &lt; 0·05). Plasma β-endorphin concentrations also showed a gradual rise (P &lt; 0·001) towards parturition; however no treatment differences were seen. These results suggest that the pituitary-adrenal (PA) axis is stimulated during pre-farrowing activity irrespective of farrowing environment. Crates, without bedding, further stimulate the PA axis over the pre-farrowing period perhaps by preventing nest-building. The rise in Q-endorphin may be involved in an endogenous defence against parturition pain.

Basal plasma β-endorphin in prepubertal sons of alcoholics and drug addicts: lack of association with problem behaviors

Several reports have speculated that variations in β-endorphin functioning may actually proceed the development of alcoholism and other drug use disorders, and is consequently a genetic mechanism of some etiologic importance. The goal of this investigation was to determine whether differences in basal plasma β-endorphin concentrations could be confirmed in prepubertal children naive to alcohol and drugs, yet at parental risk for alcoholism, or drug dependence. Consequently, we have examined fasting basal plasma β-endorphin concentrations in a sample of prepubertal sons of alcoholic fathers and compared them to both our existing sample of sons of drug dependent fathers and normal control boys. In addition, we examined the relationship between plasma β-endorphin concentrations and maternal reports of problem behaviors posited to be related to the liability for alcoholism or drug abuse. The results reveal no differences in fasting basal plasma β-endorphin concentrations. Although the at-risk groups differ significantly from normal boys having elevated scale scores for internalizing and externalizing problem behaviors, no association between plasma β-endorphin and these behavioral risk factors could be found. Overall, the results fail to support an inherited `opioid deficiency hypothesis' for the development of alcoholism or drug dependence.

Plasma concentrations of β-endorphin in trained eumenorrheic and amenorrheic women

Objective: To characterize the pattern of plasma β-endorphin throughout the normal menstrual cycle and test the hypothesis that β-endorphin concentrations are elevated in trained women with amenorrhea compared with trained and sedentary eumenorrheic women. Design: Cohort analytic study. Setting: Academic research environment. Participants: Healthy female volunteers: 10 eumenorrheic sedentary, 11 eumenorrheic trained, and 11 amenorrheic trained women. Interventions: Blood samples were collected three times per week for either one complete menstrual cycle (eumenorrheic sedentary and trained subjects) or for a 4-week period (amenorrheic trained subjects). Main Outcome Measure: Plasma β-endorphin concentrations. Results: β-Endorphin levels varied considerably across the sampling period and were not associated with menstrual status, gonadotropin, or gonadal steroid concentrations. Average β-endorphin levels were not different between the follicular and luteal phases for menstruating subjects, but were greater in the eumenorrheic athletes. Compared with eumenorrheic sedentary subjects, plasma β-endorphin levels were higher in the athletic groups, regardless of menstrual status. Conclusion: There were no cycle-related β-endorphin changes. Eumenorrheic and amenorrheic athletes have higher β-endorphin concentrations that may reflect adaptations to intense training and not exercise-associated amenorrhea.

Plasma β-endorphin, ACTH and cortisol concentration in children with early onset epilepsy

Plasma β-endorphin, ACTH and cortisol concentration in children with early onset epilepsy

Associations of beta-endorphin with HVA and MHPG in the plasma of prepubertal boys: effects of familial drug abuse and antisocial personality disorder liability

It is well-established that the secretion of the opioid neuropeptide β-endorphin is perturbed by the administration of various drugs of abuse. Several investigators have speculated that variations in β-endorphin secretory regulation may precede the development of a substance use disorder, and thus be a component of the liability for substance abuse. In order to test this hypothesis, we examined fasting, morning plasma concentrations of β-endorphin and two catecholamine metabolites in prepubertal boys naive to drugs of abuse and at elevated familial risk for a substance use disorder (SA+), and in controls (SA−). Specifically, the dopaminergic metabolite homovanillic acid (pHVA), and the noradrenergic metabolite, 3-methoxy-4-hydroxy-phenylglycol (pMHPG) were measured. Between-group differences were not found for β-endorphin, pHVA, or pMHPG. Similarly, such differences did not differentiate sons of fathers with Antisocial Personality Disorder and controls. However, regression analysis revealed that although both pHVA and pMHPG predicted β-endorphin concentrations to similar degrees, the directions of influence were the opposite. pHVA was found to be positively associated with β-endorphin while pMHPG was found to be negatively associated with β-endorphin. No between-group differences in these relationships were found. The results suggest an opponent process in catecholaminergic regulation of β-endorphin in humans, and are consistent with observations in the central nervous system of animal models.

Endogenous oploid peptides stimulate post-exercise insulin response to glucose in rats.

Exercise is associated with profound changes in glucose metabolism and insulin secretion. Endogenous opioid peptides may be involved in these metabolic adaptations. To gain insights into this hypothesis, we studied the effects of the opioid antagonist naloxone on the insulin response to glucose after a 2.5 h exercise bout, either by means of an intravascular glucose tolerance test in male Wistar rats or from rat islets of Langerhans isolated just after exercise. There was a tenfold increase in plasma beta-endorphin concentrations (9.8 +/- 2.1 vs. 114.2 +/- 22.0 fmol/ml, p < 0.001) in animals killed immediately after exercise. The in vivo post-exercise peak insulin response to glucose was markedly reduced compared to resting controls (p < 0.01). Interestingly, naloxone (10 mg/kg) still further decreased the insulin response compared to saline injected exercised rats (p < 0.05), but did not alter the response from resting animals. The post-exercise insulin response to 8.3 mM glucose was significantly reduced compared to resting rat islets (p < 0.05) and was further inhibited when naloxone (10 mu M) was added to the culture medium (p < 0.05). In another experiment, we also tested the effect of 10(-8) and 10(-6) M beta-endorphin on control islets. Both concentrations of beta-endorphin significantly increased the islet insulin response to 8.3 mM glucose (p < 0.05) and this effect was completely blocked by naloxone. These results suggest that endogenous opioid peptides participate in the physiological adaptation to exercise stress in maintaining post-exercise insulin response to glucose.

Defective endogenous opioid response to exercise in type I diabetic patients

Plasma β-endorphin (β-E) concentration was determined before, during, and after a standardized incremental exercise test to maximal capacity in eight type I diabetic patients and eight normal control subjects. Diabetic patients were studied under normoglycemic and hyperglycemic conditions in a single-blind random fashion to differentiate between the effects of acute hyperglycemia and of diabetes per se on the β-E response to exercise. The perceived magnitude of leg effort elicited by exercise was evaluated using a category scale. Whereas plasma β-E concentrations increased in control subjects with increasing workload, causing significantly higher β-E levels at the end of exercise than at the beginning ( P < .001), no such increase could be observed in the diabetic patients under normoglycemic and hyperglycemic conditions. In addition, baseline plasma β-E concentrations were significantly lower in normoglycemic ( P < .01) and hyperglycemic ( P < .001) diabetic patients than in control subjects. Even during the recovery period, patients' β-E levels remained significantly lower than those of control subjects. At submaximal levels of power output, the perceived intensity of leg effort was significantly higher in normoglycemic and hyperglycemic diabetic patients than in control subjects. We conclude that in type I diabetic patients, the ability of the endogenous opioid system to respond to exercise-induced stress is impaired under hyperglycemic and even under normoglycemic conditions. Considering the effect of endogenous opioids on stress tolerance, such changes may compromise exercise performance in diabetic patients.