Impairment of adrenergic-induced proopiomelanocortin-related peptide release in heroin addicts

The effects of iv stimulation with clonidine on plasma levels of beta-lipotropin (beta-LPH), beta-endorphin (beta-EP), cortisol, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) were tested in a group of 10 healthy volunteers and in 8 heroin abusers. Hormones were measured either by direct radioimmunoassay (RIA) (GH, cortisol) or after plasma extraction and Sephadex G-75 column chromatography (beta-LPH and beta-EP) or by immunoradiometric assay (IRMA) (ACTH). Plasma levels of GH increased in a similar fashion in the two groups. In the controls, clonidine induced release of beta-LPH and beta-EP after 30 min (from 8.9 +/- 1.0 to 19.1 +/- 4.6 fmol/ml, P less than 0.01 and from 8.1 +/- 0.6 to 17.9 +/- 4.6, P less than 0.01) and of ACTH after 60 min (from 12.1 +/- 1.8 to 18.1 +/- 1.8, P less than 0.05) while in addicts beta-EP but not beta-LPH showed a significant increase (from 8.5 +/- 0.7 to 19.8 +/- 4.2, P less than 0.05), 90 min after the injection. In heroin addicts, plasma cortisol levels decreased continuously after clonidine stimulation while in controls they showed a biphasic pattern, decreasing until the 60th min (from 135.2 +/- 30.4 ng/ml to 74.0 +/- 13.3, P less than 0.05) and regaining basal levels 1 h later (122.0 +/- 24.8, P less than 0.05 vs 60th min value). These data demonstrate the existence in human beings of noradrenergic control of proopiomelanocortin (POMC)-related peptides and indicate that chronic opiate abuse greatly interferes with this control. Clonidine-induced release of plasma beta-EP may be of importance with regard to its therapeutic effects in detoxification.     

Serotoninergic agonists increase plasma levels of beta-endorphin and beta-lipotropin in humans

A pharmacological approach was used to investigate the serotoninergic control of plasma levels on beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) in humans. Acute administration of L5-OH-triptophan, the physiologic precursor of serotonin (SE), induced a significant rise in plasma beta-EP and beta-LPH levels both when injected iv (20 and 40 mg) (four normal men) and when administered orally (200 and 400 mg) (seven normal men) (P less than 0.01 vs. placebo). The iv route of administration induced a prompt (mean peak values after 150 min) dose-dependent increase in beta-EP and beta-LPH levels. The responses evoked by oral administration (mean peak values after 130 and 240 min) were not dose dependent. Fluoxetine (15 and 30 mg orally) a blocker of SE reuptake, induced a significant dose-related rise in plasma beta-EP and beta-LPH levels in a group of seven normal men (P less than 0.01) (mean peak values after 150 min). Pretreatment with methysergide, a SE receptor antagonist (3 X 2.8 mg orally, five men), did not induce any significant changes in plasma beta-EP and beta-LPH levels, but blocked the increase in the two hormones evoked by L5-OH-triptophan (40 mg iv). Plasma cortisol levels changed similarly to those of beta-EP and beta-LPH in all the experiments, indicating that putative serotoninergic drugs exert a positive role on the various corticotropin-releasing hormone-mediated secretions.     

Effects of sodium valproate and diazepam on beta-endorphin, beta-lipotropin and cortisol secretion induced by hypoglycemic stress in humans

Evidence that gamma-aminobutyric acid (GABA) and benzodiazepine receptors play a role in the inhibition of ACTH-cortisol secretion in humans has until now been drawn only from data indicating that sodium valproate, a GABA mimetic, and diazepam, a benzodiazepine, decrease hypothalamus-pituitary-adrenal (HPA) axis secretion in patients affected by pathological hypersecretion of the axis. Therefore, the present study investigated the effects, in the same healthy subjects, of sodium valproate or diazepam, on both basal and stress-stimulated concentrations of beta-endorphin (beta-EP), beta-lipotropin (beta-LPH) and cortisol. A single maximal dose of sodium valproate (400 mg) or diazepam (10 mg) did not significantly modify basal concentrations of beta-EP, beta-LPH and cortisol. On the other hand, in the same subjects, pretreatment with sodium valproate (20 mg X 3) or diazepam (10 mg X 2) blocked the increases in these hormones produced by hypoglycemic stress in all patients tested (p less than 0.01 vs. placebo at 45, 60 and 90 min after insulin injection), without affecting the decrease in blood glucose levels. The present data show that sodium valproate and diazepam inhibit stress-induced beta-EP, beta-LPH and cortisol secretion in humans, suggesting that endogenous GABA and benzodiazepine receptors participate in physiological mechanisms regulating the activity of the HPA axis.     

SOMATOSTATIN AND OXYTOCIN INFUSION INHIBITS THE RISE OF PLASMA β-ENDORPHIN, β-LIPOTROPHIN AND CORTISOL INDUCED BY INSULIN HYPOGLYCAEMIA

The present study investigated the possible effect of somatostatin and oxytocin on the basal and stress-induced rise of beta-endorphin (beta-END), beta-lipotrophin (beta-LPH) and cortisol in the human. For this purpose somatostatin (4.1 micrograms/min for 120 min or oxytocin (0.4 micrograms/min for 120 min) was infused into two different groups of seven healthy subjects; 30 min after the start of the infusion, placebo or insulin (0.1 IU/kg body weight, B.W.) was injected on two different days. In a third experimental step, an insulin tolerance test was performed during saline infusion to evaluate stress-related effects on the different hormonal secretions under basal conditions. Plasma levels of beta-END, beta-LPH and cortisol were measured by radioimmunoassay. Extraction and chromatographic procedures preceded the assay for beta-END and beta-LPH. Neither somatostatin nor oxytocin significantly modified basal plasma levels of beta-END, beta-LPH and cortisol. However these treatments blunted the rise of the three hormones seen at 45 and 60 min during insulin-induced hypoglycaemia (P less than 0.01). These results indicate that somatostatin and oxytocin may influence the beta-END, beta-LPH and cortisol increase induced by stress in humans, without affecting their basal secretion.     

Beta-lipotropin and beta-endorphin in physiological and surgical menopause

Beta-lipotropin (beta-LPH) and beta-endorphin (beta-EP) plasma levels were characterized by a significant decrease in postmenopausal females (22 subjects aged from 56 to 70 yr) when compared to fertile women (22 subjects from 31 to 45 yr). On the contrary, ACTH plasma levels determined in 10 of the premenopausal and 13 of the postmenopausal subjects reported above showed constant levels in both groups. A significant increase in the beta-LPH/beta-EP molar ratio was observed in postmenopausal females. The plasma beta-LPH and beta-EP levels studied before and 6 months after ovariectomy, showed a significant decrease in 8 out of 10 patients, while they remained constant in the other 2. Two subjects, in whom postsurgical samples were taken during a flushing episode, showed beta-LPH and beta EP plasma levels which were both higher than the corresponding preovariectomy values. The results suggest that these changes may be important in explaining modifications in behavior and mood frequently found in postmenopausal females and in patients undergoing surgical castration in the fertile age.     

PLASMA IMMUNOREACTIVE β-ENDORPHIN IS ELEVATED IN URAEMIA

Plasma immunoreactive-(IR) beta-endorphin (beta-EP) and beta-lipotrophin (beta-LPH) levels were measured in 15 adult uraemic patients on chronic haemodialysis. The presence of immunoreactivity eluting in the position of beta-EP was demonstrated following submission of pooled extracts of uraemic plasma to gel permeation chromatography on Sephadex G-50. To separate beta-EP from beta-LPH, pre-dialysis plasma extracts from six individual patients, and three pools of three patients each, were submitted to sequential immune-affinity chromatography and levels were measured by radioimmunoassay. In all cases, plasma IR beta-EP concentrations were markedly increased compared with normal subjects (m +/- SEM fmol/ml; 64.4 +/- 13.7 vs. 2.3 +/- 0.2). IR beta-LPH concentrations were also increased (m +/- SEM fmol/ml; 55.7 +/- 13.2 vs. normal 6.1 +/- 0.8). In addition, post-dialysis concentrations of plasma IR beta-EP and beta-LPH were lower than pre-dialysis levels (n = 4).     

gamma-Aminobutyric acid inhibits beta-endorphin secretion from the anterior pituitary but not the neurointermediate lobe in the rat

We have evaluated the role of gamma-aminobutyric acid (GABA) in the neuroendocrine control of beta-endorphin (beta-EP) secretion in the rat. Plasma beta-EP and beta-lipotropin (beta-LPH) levels and beta-EP-like immunoreactivity (beta-EPLI) in the anterior pituitary (AP) and neurointermediate lobe (NIL) were determined after administration of GABA antagonist or agonist drugs in male rats under resting conditions or after potent physical stresses. Bicuculline (0.1-0.8 mg/kg BW ip), a GABA receptor antagonist, induced a dose-related rise in plasma beta-EP and beta-LPH levels and a concomitant decrease in beta-EPLI concentrations in the AP but not in the NIL. Muscimol, a potent GABA-mimetic drug, did not alter baseline plasma beta-EP and beta-LPH levels, whether given systemically (1.0-2.0 mg/kg BW ip) or intracerebroventricularly (500 ng/kg BW), but prevented the effect of bicuculline on plasma and AP-beta-EP and beta-LPH concentrations. Administration of foot shock or restraint stress induced a clear-cut activation of the AP-related beta-EP secretion, an effect that was prevented by pretreatment with muscimol. Together, these data show that GABA-ergic mechanisms, probably operating at a central nervous system level, exert an inhibitory action on resting and stimulated beta-EP and beta-LPH secretion. Since no alterations in beta-EP concentrations in the NIL occurred after manipulations with GABA-ergic drugs or stress, and these were detected only in the AP, an interaction between GABA-ergic neurons and CRF neurons is the most likely explanation for the reported findings.     

Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts

The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, beta-lipotrophin, (beta-LPH), beta-endorphin (beta-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (beta-LPH and beta-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a.m. the next morning. The means of the two 8 a.m. measurements of beta-LPH (2.67 +/- 0.34 fmol/ml, mean +/- SE), ACTH (2.74 +/- 0.71) and cortisol (218 +/- 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 +/- 0.61, 10.1 +/- 0.74 and 364 +/- 27, respectively, P less than 0.01) while beta-EP concentrations in heroin addicts (5.1 +/- 0.6) were similar to those of healthy volunteers (6.44 +/- 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.(ABSTRACT TRUNCATED AT 250 WORDS)     

GH responses to a near-maximal exercise training session on-the-field in cyclists

Acute plasma GH response to prolonged (1 h) near-maximal exercise was studied in 7 elite cyclists (6 males, 1 female; mean age +/- SE: 24.9 +/- 1.4 yr) during a routine training session on an uphill track (length: 22.0 km, average slope: 4.39%) and during a recovery (REC) period of 60 min from the end of exercise. The training session entailed a warming-up (WARM) phase of about 20 min at 63% of individual maximal heart rate (HRmax) followed by a high intensity exercise (HIE) phase of about 60 min at 90-92% of HRmax. GH resting values averaged 0.2 +/- 0.06 ng/ml; average GH concentration attained a maximal value (21.5 +/- 3.3 ng/ml, range: 11.0-38.2 ng/ml) between 20 and 40 min of HIE and significantly decreased thereafter (p=0.01), although exercise intensity was unchanged in the following period (p=0.14). After WARM, GH concentrations were significantly lower than peak values (p=0.05). During REC, GH levels steadily decreased, attaining a value of 2.6 +/- 0.8 ng/ml 60 min after the end of exercise. It was concluded that during prolonged and sustained exercise on-the-field in cyclists, GH value determined at the end of the bout may not correspond to the maximal value, which can be observed after 20 to 40 min of near-maximal exercise.     

Exercise-induced hepatic glucose output is precisely sensitive to the rate of systemic glucose supply

It has previously been established that a glucose infusion causing hyperglycemia and alterations in the levels of glucoregulatory hormones suppresses the exercise-induced increment in systemic glucose appearance (Ra). In an attempt to define the mechanisms responsible for this suppression of Ra, five normal subjects were exercised for 60 minutes on a bicycle ergometer at 60% Vo2 max on two occasions. On both occasions Ra was measured by a nonsteady state technique using a constant infusion of 3-3H-glucose. On the second occasion, an IV infusion of glucose was administered in a stepwise fashion to simulate in timing and magnitude the measured Ra response from the first study. Endogenous glucose production in the second study, estimated by subtracting the amount of glucose infused from the measured Ra response, did not increase above basal (endogenous glucose output response = 0.5 +/- 8.4 mmol/60 min v control study 60.2 +/- 6.6 mmol/60 min, P less than 0.01). The suppression of Ra was associated with a small but significant effect on venous plasma glucose (increment above basal less than 0.3 mmol/L, P less than 0.05) and a significant change in glucose metabolic clearance rate during the second 30 minutes of exercise. Serum insulin, C-peptide, cortisol, growth hormone, and plasma glucagon responses to exercise were not significantly affected by glucose infusion and the ratio of circulating insulin to glucagon was also not affected. These results indicate that hepatic glucose output during exercise is precisely sensitive to glucose supply. The feedback inhibition is presumably mediated by a small increase in plasma glucose but cannot readily be accounted for by changes in glucoregulatory hormones.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of naltrexone treatment on the treadmill exercise-induced hormone release in amenorrheic women.

The effect of an acute physical stress on hormone secretions before and after a 10-day naltrexone treatment in untrained healthy and amenorrheic women was investigated. Plasma levels of pituitary (LH, FSH, prolactin, GH, ACTH, beta-endorphin) and adrenal (cortisol, androstenedione, testosterone) hormones were measured at rest and in response to 60 min of physical exercise. The test was done both before and after a 10-day naltrexone (50 mg/day) treatment. Graded levels of treadmill exercise (50, 70 and 90% of maximal oxygen uptake (VO2) every 20 min) was used as physical stressor. While mean +/- SE plasma LH levels in control women were higher than in amenorrheic patients and increased following the naltrexone treatment (p < 0.01), no significant differences of basal plasma hormonal levels were observed between amenorrheic and eumenorrheic women, both before and after naltrexone treatment. Physical exercise at 90% VO2 induced a significant increase in plasma GH, ACTH, beta-endorphin, cortisol, androstenedione and testosterone levels in controls before naltrexone treatment (p < 0.01). The mean increase in plasma androstenedione and testosterone levels in control women was significantly higher after naltrexone treatment (p < 0.01). In amenorrheic patients before naltrexone, physical exercise induced an increase in plasma prolactin and GH levels, but not in plasma ACTH, beta-endorphin, cortisol, testosterone and androstenedione. After naltrexone treatment, the exercise induced a significant plasma ACTH, beta-endorphin and cortisol levels, while the increase of plasma prolactin levels was significantly higher than before treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorespiratory response to exercise before and after acute beta-adrenoreceptor blockade in nonsmokers and chronic smokers

To evaluate the effects of chronic smoking on exercise performance we studied 5 smokers and 7 nonsmokers of comparable age and physical characteristics. The resting heart rate in smokers (75 +/- 3 beats/min; mean +/- SD) was significantly (P less than 0.01) higher than in nonsmokers (64 +/- 5). During exercise on a bicycle ergometer the heart rate remained significantly (P less than 0.01) higher in smokers than in nonsmokers. After exercise, the heart rate in nonsmokers settled to 78 +/- 9 beats/min at 10 minutes compared with 105 +/- 11 (P less than 0.01) in smokers. Oxygen consumption was similar in both groups throughout. Beta-adrenergic blockade reduced the exercise tachycardia in both groups but the heart rate for the same workload remained significantly (P less than 0.01) higher in smokers. Beta-blockade significantly reduced (P less than 0.05) oxygen consumption in nonsmokers but not in smokers who also incurred a significantly (P less than 0.05) greater oxygen debt and had higher serum lactate levels. These differences were attributed mainly to carboxyhaemoglobinaemia and partly to the effect of prolonged smoking on the heart and on intermediary metabolism.     

Free fatty acids inhibit adrenocorticotropin and cortisol secretion stimulated by physical exercise in normal men

BACKGROUND: The basal circulating levels of ACTH and cortisol, but not the ACTH/cortisol response to hCRH, are significantly reduced by free fatty acid (FFA) infusion. OBJECTIVE: To verify whether FFA infusion modifies the ACTH/cortisol response to physical exercise, a well-known activator of the HPA axis at suprapituitary level. DESIGN: Exercise tests on a bicycle ergometer during infusion of a lipid-heparin emulsion (LHE) (experimental test) or normal saline (NaCl 0.9%) (control test). SETTING: Department of Cardiology at the University-Hospital. SUBJECTS: Seven healthy male subjects aged 25-33 years. INTERVENTIONS: On two mornings, at weekly intervals, LHE or saline were infused for 60 min; infusion started 10 min before exercise test on a bicycle ergometer, which lasted about 15 min. MAIN OUTCOME MEASURES: Circulating ACTH/cortisol levels and physiological variables during physical exercise. RESULTS: FFA levels (0.4 +/- 0.1 mEq/l) remained constant during control test, whereas they progressively rose (peak at 60 min, 2.7 +/- 1.0 mEq/l) during LHE infusion. Neither basal nor exercise-induced changes in physiological variables were modified by LHE infusion. Both ACTH and cortisol increased during exercise, with peak levels at 20 min and 30 min (control test: 103% and 42%, P < 0.001; experimental test: 28.5% and 18.6%, P < 0.05 higher than baseline, respectively). Both ACTH and cortisol responses were significantly lower in the experimental than in the control test (at 20 min P < 0.002 and at 30 min P < 0.05 for ACTH; at 20 min P < 0.05 and at 30 min, 40 min and 50 min P < 0.001 for cortisol). CONCLUSIONS: These data represent the first demonstration of an inhibitory action of increased circulating FFA levels on the HPA axis under stimulatory conditions (i.e. physical exercise, a challenge acting at suprapituitary level). In contrast, previous studies did not show FFA effects on the CRH-induced ACTH/cortisol response. Therefore, our data suggest negative effects of FFAs on the HPA axis at hypothalamic or higher centres in the central nervous system.     

Echocardiographic assessment of myocardial performance after prolonged strenuous exercise.

To determine the effect of strenuous prolonged exercise on systolic and diastolic left ventricular function, 11 non-elite marathon runners aged 37 +/- 7 years (mean +/- SD) were studied before and during early recovery from a marathon race. Cavity dimensions, wall thickness, and fractional shortening were computed from two-dimensionally guided M-mode echocardiograms. Doppler left ventricular inflow tract recordings were analysed for peak early and late velocities and their ratio. In seven subjects, heart frequency was recorded throughout the race. These subjects ran the marathon at 87 +/- 4% of their maximal heart rate. Left ventricular diastolic dimension was slightly reduced at the end of the race (49.4 +/- 4.2 mm to 47.3 +/- 5.1 mm; P less than 0.05). Fractional shortening remained unchanged, although blood pressure (P less than 0.001) and systolic wall stress (P less than 0.01) were decreased. The left ventricular filling pattern was unchanged, and the ratio of early to late velocities remained constant. These results suggest that the fractional shortening was a result of the opposing effects of changes in preload and afterload. However, the absence of a change in the end systolic dimension, despite a marked reduction in afterload and the occurrence of septal akinesia in one subject after the race could only suggest that strenuous prolonged exercise may alter myocardial performance.     

Relationship Between Plasma Catecholamines and the Renin-Aldosterone System During Exercise in Normal and Essential Hypertensive Subjects

Interrelations were investigated between blood pressure, plasma epinephrine (E), norepinephrine (NE), dopamine (D), aldosterone, cortisol concentrations, active and inactive plasma renin activity (PRA), and age in 21 normotensive subjects (aged 20–60 years) and in 25 patients (aged 20–63 years) with essential hypertension (EH). These parameters were measured at rest and during exercise on a bicycle ergometer. In normotensive subjects basal and exercise-stimulated levels of plasma NE increased with age which was not observed in EH. In hypertensive patients there was a higher plasma D concentration under the exercise as compared with normotensive controls. In the normotensives, basal active PRA was inversely related to age (p<0.05), and during initial 8 min of exercise active PRA significantly correlated with plasma E and plasma NE. Moreover, absolute changes from basal to acutely stimulated values of active PRA were directly related to the changes of plasma E and NE (p<0.001). In hypertensive patients these relationships were not found. However, in the hypertensives there were significant positive correlations between the increases of active PRA, plasma E, plasma NE on the one hand and their respective basal values on the other hand.

The results indicate very strong functional relationship between the sympathetic-adrenomedullary and renin-angiotensin systems during initial interval of acute stimulation in normotensive subjects. Essential hypertension is not a pathophysiologically homogenous disease with respect to reactivity and interaction of plasma catecholamines and PRA. Separate regulatory pathways exist for plasma active and inactive renin. During short-time exercise aldosterone secretion is related rather to the renin-angiotensin system than to the hypothalamic-pituitary axis.     

Plasma malondialdehyde in coronary patients and in "normal" people at rest and after exercise

The behavior of plasma lipid peroxides, expressed as plasma malondialdehyde, was studied in 27 patients with documented coronary artery disease and 17 volunteers without coronary artery disease (henceforth designated "normal"), after a standardized exercise on a bicycle ergometer. In the control group, the basal values of malondialdehyde were significantly lower than in coronary patients. Persons in the control group did not show any significant variation of malondialdehyde after exercise and recovery, whereas patients with coronary artery disease showed malondialdehyde levels significantly higher than the baseline, both after exercise and after recovery. In the control group, a significant inverse correlation between the malondialdehyde variations during the exercise and the total work produced was ten times lower than in coronary patients. It seems probable that the higher levels of lipid peroxides in these patients may leave some long-term unwanted effects. Furthermore, the increased values of lipid peroxides after exercise may be regarded as a possible trigger of fatal myocardial malfunction occurring during physical activity.     

Dramatic elevations of interleukin-6 and acute-phase reactants in athletes participating in the ultradistance foot race spartathlon: severe systemic inflammation and lipid and lipoprotein changes in protracted exercise

CONTEXT AND OBJECTIVE: Plasma IL-6, the serum inflammatory markers C-reactive protein (CRP) and serum amyloid A (SAA), and the tissue destruction marker-free plasma DNA, as well as the circulating lipid profile, were examined in athletes participating in the ultradistance foot race of the 246-km Spartathlon. SETTING, DESIGN, AND PARTICIPANTS: This race consists of continuous, prolonged, brisk exercise. Blood samples were obtained from 15 male athletes, who finished the race in less than 36 h, taken before, at the end of, and 48 h after the end of the race. RESULTS: IL-6, CRP, SAA, and free plasma DNA levels markedly increased (by 8000-, 152- 108-, and 10-fold, respectively) over the baseline at the end of the race. However, IL-6 levels returned to normal by 48 h, whereas CRP, SAA, and free plasma DNA remained elevated. The mean values of cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein B decreased to a minimum value at the end of the race and remained low 48 h after the race. High-density lipoprotein levels, on the other hand, were mildly increased at the end of the race (P < 0.015) and decreased to normal 48 h after the race. Apolipoprotein AI levels decreased significantly during the time course of the exercise and remained low 48 h after the race (P < 0.001). CONCLUSIONS: These observations suggest that continuous, prolonged, moderate-intensity exercise is associated with markedly elevated IL-6 and acute-phase reactant concentrations, peripheral tissue damage, and significant changes in serum lipid levels. The biochemical changes observed during the Spartathlon amount to a potent systemic inflammatory response, which might explain severe cardiovascular events that occur during prolonged exercise in compromised individuals.     

Specific radioimmunoassay of human beta-endorphin in unextracted plasma.

With an antiserum against human beta-endorphin (beta-EP) crossreacting less than 2% with human beta-lipotropin (beta-LPH) by weight we have developed a radioimmunoassay that can detect 1 pg beta-EP in diluted raw plasma. In a.m. fasting plasma of 14 normal subjects beta-EP ranged from less than 5 to 45 pg/ml. beta-EP was elevated in untreated, but normal in successfully treated Cushing's disease; undetectable in a patient with adrenal adenoma; extremely high in Nelson's syndrome; and elevated in a patient with bronchogenic carcinoma before, but undetectable after tumor resection. In subjects with intact hypothalamic-pituitary-adrenal axis, beta-EP was undetectable after dexamethasone and increased after metyrapone administration and insulin-induced hypoglycemia. beta-EP concentration was considerably lower in serum than in simultaneously collected plasma, but increased in serum left unfrozen for several hours after clot removal. Thus, beta-EP behaves like a hormone responding to the same stimuli as ACTH and beta-LPH and blood appears to contain enzymes both generating and destroying immunoreactive beta-EP.     

Response of circulating adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol to athletic competition

Acute physical exercise stimulates the activity of the hypothalamus-pituitary-adrenal axis in man. In the present study we measured plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol levels in 27 male trained athletes in basal conditions, 60 min before and immediately after an official competition. The endocrine responses were evaluated in different groups of athletes participating in races (100 m, 1500 m, 10,000 m) or in the disc throw. The athletes competing for the runs showed a statistically significant increase in plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol levels after the race (P less than 0.01), whereas the disc throwers showed no significant change in the hypothalamus-pituitary-adrenal axis hormones after the competition. The percent increase in plasma adrenocorticotropin, beta-endorphin, beta-lipotropin and cortisol was higher in the athletes who run 1500 m and 10,000 m than in those participating in the short distance race (100 m). The present results showed that plasma proopiomelanocortin-related peptides and cortisol levels increase in trained athletes following running competition and that this increase is related to the duration of the physical exercise.     

The effects of metformin and glibenclamide on glucose metabolism, counter-regulatory hormones and cardiovascular responses in women with Type 2 diabetes during exercise of moderate intensity.

AIMS: To compare the effects of metformin and glibenclamide on cardiovascular, metabolic and hormonal parameters during exercise of moderate intensity performed in the postprandial state, in women with Type 2 diabetes. METHODS: Ten patients treated with metformin, 10 with glibenclamide and 10 control subjects (C) exercised on a bicycle ergometer at 50% of oxygen uptake (VO(2)) peak for 45 min. Cardiovascular, blood metabolic and hormonal parameters were determined at times -60 min (fasting), 0, +15, +30, +45 min (exercise) and at +60, +90 min (recovery). Thirty minutes prior to exercise, participants consumed a standard breakfast. Patients with diabetes took metformin or glibenclamide before the meal. RESULTS: Systolic and diastolic blood pressure and plasma glucose were higher in both diabetic groups, for the whole experiment. Blood glucose did not change during exercise in the three groups and increased at recovery only in the control group. Plasma glucagon concentrations at the end of exercise and recovery, and plasma lactate concentrations at recovery were higher in the metformin group. Insulin, noradrenaline, growth hormone, cortisol and free fatty acid responses were similar in all three groups. CONCLUSIONS: Our results suggest that the usual dose of glibenclamide and metformin can be taken safely before postprandial exercise of moderate intensity without affecting cardiovascular, metabolic and hormonal responses. However, after exercise, glibenclamide and metformin prevent the normal rise in blood glucose and metformin delays the fall in plasma lactate concentrations.