Effect of nicotine on in vivo secretion of melanocorticotropic hormones in the rat

Corticosterone, ACTH, β-endorphin and α-MSH were measured in rat plasma by radioimmunoassay before and 2,5,15,30 minutes after an intraperitoneal injection of nicotine (500 μg/Kg b.w.). Nicotine induced an increase of plasma corticosterone (p < 0.05 at t + 15 min), ACTH and β-endorphin (p < 0.01 at t + 5 min) and a decrease of α-MSH (p < 0.005 at t + 15 min). Dose response experiments showed an increase of corticosterone, ACTH, β-endorphin 15 min after 250 μg/Kg b.w. nicotine I.P., no effect being observed after injection of 100 μg/Kg b.w. The decrease of α-MSH was observed 15 min after 100, 250 or 500 μg/Kg b.w. nicotine I.P. Our results suggest that the increase of corticosterone is mediated through ACTH release.     

Effect of beta-endorphin on the steroid production of isolated zona glomerulosa and zona fasciculata cells

Small doses of β-endorphin (10^?11?10^?5M) decrease corticosterone production of zona fasciculata cells but fail to influence steroid production of zona glomerulosa cells. 10^?4M β-endorphin increases corticosterone production of both zones. The stimulating effect of ACTH on zona fasciculata corticosterone- and zona glomerulosa aldosterone production was decreased by β-endorphin (10^?9?10^?7M). Conclusion: β-endorphin might modulate both basal and ACTH stimulated corticosterone secretion.     

Plasma vasopressin, growth hormone and ACTH responses to static handgrip in healthy subjects

Ten healthy male subjects took part in the study. They performed three consecutive bouts of static handgrip at 30% of maximal voluntary contraction (MVC), using two hands alternately and without rest intervals. Blood pressure was measured every 30 s and ECG was recorded continuously. Blood samples for arginine vasopressin (AVP), growth hormone (GH), adrenocorticotrophic hormone (ACTH) and cortisol determinations were taken at rest, after each exercise bout, as well as at 10 and 30 min after the last one. During the whole period of exercise (9 min) blood pressure and heart rate were elevated. The effort caused a significant increase in the plasma AVP concentration. In the majority of subjects the peak values occurred after the first or second exercise bout and were followed by a rapid decline of the hormone concentration. Changes in GH, ACTH and cortisol concentrations were insignificant; however, in seven of the ten subjects, considerably elevated plasma GH levels were found at the end of the third exercise bout and/or 10 min after its cessation.     

Effect of prolonged exhausting exercise on the adrenal cortex response to ACTH

Plasma cortison response of ACTH injection was studied in dogs under control conditions and after a prolonged exercise performed until exhaustion. Exercise induced a marked increase in plasma cortisol concentration but no significant differences were found in the level of plasma cortisol following ACTH injection between the control and post-exercise animals.     

Functioning of the pituitary-adrenal system during the vestibulo-vegetative syndrome and administration of dalargin and nalorphine

Changes in ACTH, cortisol, beta-endorphin have been investigated during vestibulo-vegetative syndrome (VVS) and injections of dalargin (leu-enkephalin analog) and nalorphine (agonist-antagonist of opioid receptors) in 9 volunteers with low level vestibulo-vegetative stability. Cumulative coriolis acceleration test during rotations on a special chair was used for VVS modelling. Dalargin (1-4 mg), nalorphine (5 mg) and placebo (NaCl solution) were injected intravenously 5-15 min before rotation. A significant increase in ACTH, cortisol and beta-endorphin plasma levels has been observed. Mean positive linear correlation (r greater than +0.6) between ACTH and beta-endorphin and ACTH and cortisol was noted immediately after the test only when dalargin was injected. It is suggested that in VVS there develops a hormonal conflict, i. e. an adequate hormonal release is disturbed.     

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。     

Biosynthesis of beta-endorphin, beta-lipotropin and the putative ACTH-LPH precursor in the frog pars intermedia.

When frog pars intermedia are incubated for 3 h with radioactive methionine, the predominant labeled peptide is one with an apparent molecular weight of 33, 100. This peptide can be immunoprecipitated with antisera against β-melanotropin (β-MSH), adrenocorticotrophin (ACTH), and β-endorphin and is believed to be the common precursor of ACTH and β-lipotropin (β-LPH). Immunoprecipitation experiments have also demonstrated the presence of labeled β-LPH and β-endorphin. The labeled β-endorphin has been shown to behave identically to sheep β-endorphin on both carboxymethyl-cellulose chromatography and polyacrylamide gel electrophoresis. Frog β-endorphin has methionine as the fifth residue, as do all other β-endorphins that have been sequenced.     

Development of the pituitary-adrenal axis in chronically cannulated ovine fetuses

In the intact, unstressed ovine fetus, both plasma immunoreactive adrenocorticotrophin (ACTH) and blood cortisol concentrations increased after 121 days gestation. The mean ACTH and cortisol concentrations in intact fetuses of 90-121, 122-135 and 136-144 days gestation were for ACTH 20.4 +/- 3.9 (50) (mean +/- SEM, n), 30.2 +/- 5.6 (26) and 56.0 +/- 6.3 pg/ml (37) respectively, and for cortisol 0.07 +/- 0.01 (24), 0.17 +/- 0.03 (21) and 0.64 +/- 0.13 microgram/100 ml (15), respectively. After 121 days ACTH and cortisol concentrations were correlated positively. Cortisol infused into intact or adrenalectomized fetuses and corticosterone infused into adrenalectomized fetuses suppressed fetal plasma ACTH concentrations. In summary, ACTH and cortisol increase concomitantly after 122 days, so that it is highly probable that ACTH is the trophic stimulus for fetal adrenal maturation. The suppression of ACTH by cortisol and corticosterone suggests that these are the natural feedback regulators. It is proposed that while the mechanism for cortisol feedback may exist early in gestation, it is not until after 121 days that feedback control of ACTH becomes evident and physiologically important.     

The release of corticosterone and a corticosterone-binding protein by incubated rat adrenal slices

Stimulation of incubated rat adrenal slices with ACTH(1-24) resulted in an increase in the release of both corticosterone and specific corticosterone-binding protein into the incubation medium. The release of corticosterone and binding protein was dose and calcium dependent with adrenals from animals pretreated with betamethasone. While the secretion of corticosterone was continuous throughout the incubation period, there appeared to be a limit to the increase in binding capacity. The specificity of steroid binding to the adrenal protein showed a similar profile to that of corticosteroid-binding globulin (CBG) in rat serum. A Western blot analysis using anti-rat CBG as the primary antiserum, showed that the adrenal protein was not CBG. [3H]corticosterone binding with disc electrophoresis, run at 2 degrees C, gave a single peak with approximately the same Rf value for rat serum, purified CBG, and adrenal incubate; at 22 degrees C peaks were only seen for rat serum or purified CBG. The data presented provides further evidence for the existence of a specific corticosterone-binding protein of adrenal origin released in conjunction with corticosterone. The adrenal protein would appear to have a lower affinity for corticosterone than does CBG, and to be functionally more labile. It is possible that the adrenal protein may be CBG that has been internalized, modified and released with corticosterone.     

Effects of 2-bromo-α-ergocryptine on β-endorphin-induced growth hormone,prolactin and luteining hormone release in urethane anesthetized rats

Adult male rats were injected intraperitoneally either with saline or 2-Br- α-ergocryptine(CB-154)(10 ng/0.5 ml/rat) 30 min prior to an intraventricular injection of saline or β-endorphin (1 μg/10 μl or 5 μg/10 μl) and 30 min after β-endorphin, they were sacrificed by decapitation. Intraventricular injection of β-endorphin elicited significant increases in serum GH, prolactin and LH levels in a dose-related manner. Pretreatment with CB-154 inhibited the release of GH, prolactin and LH induced by β-endorphin. These results indicate that the stimulatory effects of β-endorphin on GH, prolactin and LH may be involved in an inhibition of dopaminergic mechanism in the central nervous system.     

Plasma cortisol and corticosterone concentrations in the golden hamster, (Mesocricetus auratus)

Because some recent studies of hamster adrenocortical function have depended on older studies that may have been inadequate or misinterpreted, the present study re-examined plasma corticosterone and cortisol concentrations in hamsters under several conditions to determine which plasma glucocorticoid predominated in this animal. Sensitive radioimmunoassays were used to measure separately the two glucocorticoids in the basal condition, after adrenocorticotropin (ACTH) treatment, after acute stress, and after chronic stress. In the basal condition, corticosterone concentrations were 3-4 times higher than those of cortisol. After stimulation, this difference disappeared, but rarely were any hamster's cortisol levels higher than their corticosterone levels. Both ACTH and acute stress elevated plasma corticosterone and cortisol concentrations, but only plasma cortisol concentrations were elevated following chronic stress. The dissociation between cortisol and corticosterone concentrations after chronic stress suggests that the two glucocorticoid hormones in the hamster may be regulated independently. The data also indicate that both corticosterone and cortisol should be measured when assessing adrenocortical function in the hamster.     

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.     

Oral arginine attenuates the growth hormone response to resistance exercise.

This study investigated the combined effect of resistance exercise and arginine ingestion on spontaneous growth hormone (GH) release. Eight healthy male subjects were studied randomly on four separate occasions [placebo, arginine (Arg), placebo + exercise (Ex), arginine + exercise (Arg+Ex)]. Subjects had blood sampled every 10 min for 3.5 h. After baseline sampling (30 min), subjects ingested a 7-g dose of arginine or placebo (blinded, randomly assigned). On the exercise days, the subject performed 3 sets of 9 exercises, 10 repetitions at 80% one repetition maximum. Resting GH concentrations were similar on each study day. Integrated GH area under the curve was significantly higher on the Ex day (508.7 +/- 169.6 min.ng/ml; P < 0.05) than on any of the other study days. Arg+Ex (260.5 +/- 76.8 min.ng/ml) resulted in a greater response than the placebo day but not significantly greater than the Arg day. The GH half-life and half duration were not influenced by the stimulus administered. The GH secretory burst mass was larger, but not significantly, on the Arg, Ex, and Arg+Ex day than the placebo day. Endogenous GH production rate (Ex > Arg+Ex > Arg > placebo) was greater on the Ex and Arg+Ex day than on the placebo day (P < 0.05) but there were no differences between the Ex and Arg+Ex day. Oral arginine alone (7 g) stimulated GH release, but a greater GH response was seen with exercise alone. The combined effect of arginine before exercise attenuates the GH response. Autonegative feedback possibly causes a refractory period such that when the two stimuli are presented there will be suppression of the somatotrope.     

Corticotropin releasing hormone and gonadotropin secretion in physically active males after acute exercise.

Plasma concentrations of corticotropin releasing hormone (CRH) and the serum concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, adrenocorticotropic hormone (ACTH) and cortisol were measured in seven physically active males after acute exercise on a treadmill using the Bruce protocol. Measurements were made in the basal pre-exercise state, immediately after exercise, and at 30-min intervals for 3 h after exercise. Serum LH concentrations declined following exercise reaching nadir values between 60 and 180 min after exercise (90 min post exercise in the group). The nadir values in individual volunteers were significantly lower than both the baseline and post-exercise levels. This fall in serum LH concentration appeared to follow a slight but significant elevation of the plasma concentration of CRH which reached peak levels when measured immediately post exercise. Plasma ACTH concentrations paralleled the rise in CRH, but fell to undetectable levels of below 13.8 nmol.l-1 (less than 5 ng.l-1) 60 min after exercise. Plasma cortisol concentrations peaked approximately 30 min after the rise in ACTH, after which they gradually declined to baseline levels. Plasma testosterone concentrations paralleled the concentrations of LH. The data suggest that CRH, on the basis of its previously described gonadotropin-depressant property, may be the hormone involved in the exercise-mediated decline in serum LH. Alternatively, some as yet unidentified factor(s), may be involved in producing the altered concentrations of both LH and CRH.     

Hypothalamic-pituitary-adrenal responses to short-duration high-intensity cycle exercise

beta-Endorphin (beta-EP), adrenocorticotropin (ACTH), and cortisol plasma concentrations were examined before and after maximal exercise at four intensities [36, 55, 73, and 100% of maximal leg power (MLP)] by means of a computerized cycle ergometer. All intensities were greater than those eliciting peak O2 uptake for the individual subjects. Blood samples were collected at rest, immediately after exercise, and at 5 and 15 min postexercise. Significant (P less than 0.05) increases were observed at 36% MLP for beta-EP and ACTH immediately after exercise and at 5 and 15 min postexercise. Plasma cortisol increased at 36% MLP at 15 min postexercise. Blood lactate significantly increased at all postexercise collection points for exercise intensities of 36, 55, and 73% MLP and at 5 min postexercise for 100% MLP. beta-EP concentrations at 36% MLP were significantly correlated (r = 0.75) with capillary density (mm-2), and cortisol concentrations at 36% MLP were significantly correlated (r = 0.89) with percentage of type II muscle fibers. No other significant relationships were observed. These data show that brief, high-intensity exercise up to maximal power production results in a nonlinear response pattern in peripheral blood hormone concentrations. Furthermore, blood lactate levels do not appear to be related to hypothalamic-pituitary-adrenal hormone plasma concentrations at high exercise intensities.     

Acute hormonal responses to heavy resistance exercise in younger and older men

The purpose of this investigation was to examine the acute responses of several hormones [total and free testosterone (TT and FT, respectively), adrenocorticotropic hormone (ACTH), cortisol (C), growth hormone (GH), and insulin (INS)] to a single bout of heavy resistance exercise (HRE). Eight younger [30-year (30y) group] and nine older [62-year (62y) group] men matched for general physical characteristics and activity levels performed four sets of ten repetitions maximum (RM) squats with 90 s rest between sets. Blood samples were obtained from each subject via an indwelling cannula with a saline lock pre-exercise, immediately post-exercise (IP), and 5, 15 and 30 min post-exercise. Levels of TT, FT, ACTH, C and lactate significantly increased after HRE for both groups. Pre-HRE pairwise differences between groups were noted only for FT, while post-HRE pairwise differences were found for TT, FT, GH, glucose and lactate. Area under the curve analysis showed that the 30y group had a significantly higher magnitude of increase over the entire recovery period (IP, 5, 15, and 30 min post-exercise) for TT, FT, ACTH and GH. Few changes occurred in the INS response with the only change being that the 62y group demonstrated a decrease IP. Lactate remained elevated at 30 min post-HRE. This investigation demonstrates that age-related differences occur in the endocrine response to HRE, and the most striking changes appear evident in the FT response to HRE in physically active young and older men. Accepted: 11 June 1997     

Molecular interpretation of ACTH-β-endorphin coaggregation: relevance to secretory granule biogenesis

Peptide/protein hormones could be stored as non-toxic amyloid-like structures in pituitary secretory granules. ACTH and β-endorphin are two of the important peptide hormones that get co-stored in the pituitary secretory granules. Here, we study molecular interactions between ACTH and β-endorphin and their colocalization in the form of amyloid aggregates. Although ACTH is known to be a part of ACTH-β-endorphin aggregate, ACTH alone cannot aggregate into amyloid under various plausible conditions. Using all atom molecular dynamics simulation we investigate the early molecular interaction events in the ACTH-β-endorphin system, β-endorphin-only system and ACTH-only system. We find that β-endorphin and ACTH formed an interacting unit, whereas negligible interactions were observed between ACTH molecules in ACTH-only system. Our data suggest that ACTH is not only involved in interaction with β-endorphin but also enhances the stability of mixed oligomers of the entire system.     

The cortisol response to ACTH in pigs,heritability and influence of corticosteroid-binding globulin

In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1–24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r_p=0.539; genetic correlation, r_g=0.938). Post-ACTH cortisol levels were highly heritable (h²=0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic–pituitary–adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but also point at pigs as a relevant model to explore the underlying mechanisms of the metabolic syndrome including the contribution of genetic factors.     

Effect of rehydration on atrial natriuretic peptide release during exercise in the heat

In an attempt to investigate their relationships with plasma volume (PV), heart rate (HR), and other hormonal systems, plasma atrial natriuretic peptide (ANP) levels were determined in response to exercise in the heat, associated with dehydration and rehydration with various fluids. Five normal subjects underwent four 3-h experiments, in a 36 degree C environment, in which 25-min exercise periods on a cycle ergometer at 90 W alternate with 5-min rest periods. Blood samples were collected hourly and ANP, arginine vasopressin (AVP), adrenocorticotropin (ACTH), and cortisol were analyzed in four experimental sessions: without fluid supplement (DH) and with progressive rehydration either with water (W), acid isotonic solution (AISO), or neutral isotonic solution (NISO). Exercise in the heat, accompanied by a decrease in PV and an increase in osmolality, elicited an increase of 28 +/- 1.6 pg/ml in plasma ANP, with concomitant increases in AVP (5.1 +/- 1.4 pg/ml), ACTH (49.6 +/- 12.3 pg/ml), and cortisol (8.4 +/- 2.0 micrograms/100 ml). Progressive rehydration maintained PV and blunted ANP, AVP, ACTH, and cortisol responses. These results demonstrate the importance of rehydration, during exercise in a warm environment, in preventing hormonal increases. They suggest that under our conditions, the PV changes and the inferred atrial pressure changes may not be the primary factors controlling ANP release, as under other physiological conditions. The exercise-related activation of pituitary and adrenals and the stimulation of HR counteract the influence of PV changes due to vascular fluid shifts.     

Effects of short-term oral salbutamol administration on exercise endurance and metabolism.

The present study examined whether oral short-term administration of salbutamol (Sal) modifies performance and selected hormonal and metabolic variables during submaximal exercise. Eight recreational male athletes completed two cycling trials at 80-85% peak O(2) consumption until exhaustion after either gelatin placebo (Pla) or oral Sal (12 mg/day for 3 wk) treatment, according to a double-blind and randomized protocol. Blood samples were collected at rest, after 5, 10, and 15 min, and at exhaustion to determine growth hormone (GH), cortisol, testosterone, triiodothyronine (T(3)), C peptide, free fatty acid (FFA), blood glucose, lactate, and blood urea values. Time of cycling was significantly increased after chronic Sal intake (Sal: 30.5 +/- 3.1 vs. Pla: 23.7 +/- 1.6 min, P < 0.05). No change in any variable was found before cycling except a decrease in blood urea concentration and an increase in T(3) after Sal that remained significant throughout the exercise test (P < 0.05). Compared with rest, exercise resulted in a significant increase in GH, cortisol, testosterone, T(3), FFAs, and lactate and a decrease in C peptide after both treatments with higher exercise FFA levels and exhaustion GH concentrations after Sal (P < 0.05). Sal but not Pla significantly decreased exercise blood glucose levels. From these data, short-term Sal intake did appear to improve performance during intense submaximal exercise with concomitant increase in substrate availability and utilization, but the exact mechanisms involved need further investigation.