Effects of treadmill running on plasma beta-endorphin,corticotropin, and cortisol levels in male and female 10K runners

Summary Reports of plasma beta-endorphin (BEN) levels in response to submaximal exercise have been highly disparate. Variations in experimental design have complicated interpretation of previous research. The present study was designed to determine whether a sequential change in plasma beta-endorphin (B-EN), corticotropin (ACTH), and cortisol levels occurs in response to a 30-min submaximal run. Twenty-three subjects were divided into four groups: male runners, female runners, sedentary males and sedentary females. Subjects ran on a treadmill at 80% of previously determined maximum heart rate. Five plasma samples were obtained through an indwelling catheter before exercise (−30 and 0 min), at 15 and 30 min of exercise, and after 30 minutes of recovery. The run resulted in no rise in B-EN, ACTH, and cortisol despite an elevated rectal temperature. B-EN values were significantly higher in males than in females (p<0.01). No sex or training differences were seen with respect to change of hormone concentrations over the course of the run. Three male runners developed symptoms of vasovagal syncope after the catheter placement and had high initial B-EN, ACTH, and cortisol concentrations which decreased throughout the run. These data indicate that gender and training do not affect ACTH and cortisol concentrations before, during, and after 30 min of treadmill running at 80% of maximum heart rate, whereas B-EN concentrations are higher in males under these conditions.     

The effects of running, environment, and attentional focus on athletes' catecholamine and cortisol levels and mood

This study was designed to examine some of the psychoneuroendocrine effects of exercise-induced emotional experiences and the mediating effects of environmental setting and subjects' attentional focus. Trained runners were tested during an outdoor run and two indoor treadmill running conditions. Excretions of catecholamines and Cortisol significantly increased after all running conditions but not after a control condition. Results indicate that patterns of endocrine and concomitant emotional change through exercise differ when environmental setting and attentional focus are altered in such a way that a normally pleasant task such as running becomes tedious and negatively evaluated. These findings support the notion that setting, attention, and cognitive appraisal may alter the emotional experience associated with physical exercise.     

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

Summary 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 (< 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.     

Safety and side effects of human and ovine corticotropin-releasing hormone administration in man

Summary Synthetic human and ovine corticotropin-releasing hormone (hCRH, oCRH) are commonly used as a diagnostic tool of the hypothalamo-pituitary-adrenal axis. In this paper reports about side effects after various modes of CRH-application are analyzed and compared to our corresponding data of human studies with hCRH and oCRH. Generally, CRH is well tolerated after single administration and interval-application of standard doses, although minor side effects appear sometimes after higher doses (>200 g hCRH, oCRH) of CRH-bolus-injections. Predominantly the cardiovascular system (e.g. tachycardia, hypotension, flushing) is affected; neuropsychological symptoms are only seen sporadically (e.g. dizziness). Long term continuous infusion (several hours) of low CRH-doses (hCRH, oCRH) are well tolerated but side effects appear (see above) when cumulated doses of 200 g–300 g/h are given. Standard doses of hCRH and oCRH are also well tolerated in severely ill patients; it has to be considered that higher doses may provoke marked side effects in persons with neurologic disorders, in subjects with coronary heart disease and in patients with endocrinological disorders of the pituitary-adrenal axis, especially in those subjects in whom the blood-brain-barrier may have been damaged (e.g. head injury, intracranial operation).Single hCRH- and oCRH-bolus-injections in standard doses have a very low rate of complications, non-standard doses should provisionally be used only in clinical studies with well designed safety-precautions.Abbreviations CRH Corticotropin-releasing hormone - hCRH human CRH - oCRH ovine CRH     

GR和ACTHR基因多态性与血脂、血糖、皮质醇以及促肾上腺皮质激素水平的相关性

目的 探讨糖皮质激素受体( glucocorticoid receptor,GR)和促肾上腺皮质激素受体(adrenocorticotropic hormone receptor,ACTHR)基因的多态性与血脂、血糖、皮质醇以及促肾上腺皮质激素(adrenocorticotropic hormone,ACTH)水平的相关性.方法 随机抽取200名健康汉族人测定血糖、血脂、皮质醇以及ACTH水平,用聚合酶链反应-限制性片段长度多态性方法测定ACTHR-2 T/C、GR 6294C/G、GR 4534 4536GAG/AAA[GAGAGG(GluArg)→GAAAAG(GluLys)]、GR 5556A/G等单核苷酸多态性.结果 GR、ACTHR基因不同基因型的血脂、血糖差异无统计学意义.GR5556A/G位点AG基因型皮质醇水平高于AA基因型.GR 4534-4536GAG/AAA AG基因型皮质醇水平高于GG基因型.GR 6294C/G位点CC和CG基因型皮质醇水平低于GG基因型.而ACTH水平只有ACTHR-2T/C TT基因型低于CC和CT基因型,GR 5556A/G位点AG基因型低于AA基因型.结论 ACTHR-2T/C、GR 5556A/G、GR 4534-4536GAG/AAA、GR 6294C/G的变异对血脂、血糖水平无影响.GR 5556A/G、GR 4534-4536GAG/AAA、GR 6294C/G 3个位点的变异可影响血清皮质醇基础水平,ACTHR-2T/C、GR 5556A/G基因位点的变异可影响血清ACTH的基础水平.     

Pituitary and adrenal hormone responses to pharmacological,physical, and psychological stimulation in habitual smokers and nonsmokers

Hormone responses to injection of corticotropin-releasing hormone following bicycle ergometry and psychological stress were studied in ten habitual smokers and ten nonsmokers. Compared to injection of saline, significant increases were found in adrenocorticotropin, prolactin, growth hormone, total serum cortisol, and salivary cortisol under all three stimulations except for salivary cortisol under ergometry. Furthermore, the smokers showed significant elevations of all five hormones investigated following the smoking of two cigarettes of the subject's preferred brand. Comparisons of hormone responses between smokers and nonsmokers revealed a general trend towards stronger responses in nonsmokers. However, due to the small number of subjects investigated and considerable variation in the individual hormone responses these differences reached statistical significance only for growth hormone responses following ergometry and salivary cortisol responses after psychological stress. In addition, the circadian rhythm of salivary cortisol was measured on two occasions between 9 a.m. and 9 p.m. in the subject's natural environment. The typical circadian pattern of decreasing cortisol levels was observed, with no significant differences between smokers and nonsmokers. We conclude that chronic nicotine consumption may lead to lower responses of multiple hormones not only to nicotine but to a variety of stimuli, and that these alterations do not necessarily affect unstimulated circadian profiles of free cortisol. Correspondence to: C. Kirschbaum     

促肾上腺皮质激素对慢性痛大鼠痛行为和海马内BDNF、CRF水平的影响

目的与方法:采用痛行为评分方法、免疫组化和原位杂交技术,观察促肾上腺皮质激素(ACTH)对完全福氏佐剂所致的关节炎大鼠海马内脑源性神经营养因子(BDNF)及其功能性受体trkB和促肾上腺皮质激素释放激素(CRH)水平的影响。结果:关节炎大鼠的痛行为评分显著高于正常对照组,同时注射侧对侧海马内BDNF免疫活性(IR)神经元、CRHmRNA阳性神经元和BDNF/CRHmRNA双染神经元数在注射佐剂后 2 4h显著高于正常对照组,而腹腔注射ACTH(2 5IU/kg或 12 5IU/kg)后,上述指标显著低于关节炎组;摘除双侧肾上腺后,腹腔注射ACTH的关节炎大鼠对侧海马内BDNF-IR、CRHmRNA阳性神经元和BDNF/CRHmRNA双染神经元数明显高于未摘除肾上腺的关节炎组。结论:海马内的BDNF和CRH参与慢性痛的调制,ACTH能抑制海马内BDNF和CRH的升高而产生镇痛作用,肾上腺对ACTH发挥其功能起决定性作用.     

Immunohistochemical analysis of the colocalization of corticotropin-releasing hormone receptor and glucocorticoid receptor in kisspeptin neurons in the hypothalamus of female rats

Kisspeptin, a neuropeptide encoded by Kiss1 gene, plays pivotal roles in the regulation of reproductive function. Recently various stressors and stress-induced molecules such as corticotropin-releasing hormone (CRH) and corticosterone have been shown to inhibit Kiss1 expression in rat hypothalamus. To determine whether CRH and glucocorticoids directly act on kisspeptin neurons, we examined the colocalization of CRH receptor (CRH-R) and glucocorticoid receptor (GR) in kisspeptin neurons in the female rat hypothalamus. Double-labeling immunohistochemistry revealed that most kisspeptin neurons in the anteroventral periventricular nucleus and periventricular nucleus continuum (AVPV/PeN), and arcuate nucleus (ARC) expressed CRH-R. We also observed a few close appositions of CRH immunoreactive fibers on some of kisspeptin neurons in AVPV/PeN and ARC. On the other hand, most kisspeptin neurons in AVPV/PeN expressed GR, whereas only a few of kisspeptin neurons in ARC expressed GR.     

Effects of nicotine and caffeine, separately and in combination, on EEG topography, mood, heart rate, cortisol, and vigilance

Effects of nicotine and caffeine, separately and in combination, were assessed in 12 male habitual smokers in a repeated-measures design. Caffeine (0-mg vs. two 150-mg doses administered in a decaffeinated/sugar-free cola drink post-baseline and 90 min later) was crossed with nicotine (ad libitum own dosing vs. 1.0-mg machine-delivered dose vs. 0.05-mg machine-delivered dose). Participants smoked a total of five cigarettes at 30-min intervals over a 2-hr period. Caffeine and nicotine had large effect sizes on electroencephalogram (EEG) power; however, these effects were modulated by the eyes open versus closed condition, the other drug, and electrode site. EEG effects of open versus closed eyes tended to be of the same size and direction as those of nicotine and caffeine. However, whereas nicotine increased EEG power in some higher frequency bands in some conditions, caffeine decreased EEG power across almost all conditions. Serum cortisol concentration, vigor, and pleasantness were increased by nicotine, but not by caffeine. Level of depressive mood depended on an interaction of caffeine and nicotine. Vigilance performance was enhanced significantly by caffeine and was increased almost significantly by nicotine. The findings were interpreted in terms of common and differential mechanisms of the two drugs.     

Increased numbers of activated mast cells in endometriosis lesions positive for corticotropin-releasing hormone and urocortin

PROBLEM: Mast cells are critical in allergic and inflammatory diseases such as interstitial cystitis, which is often clinically associated with or mistaken as endometriosis. Mast cells had previously been reported to be increased at sites of endometriosis, and tryptase may contribute to the fibrosis and inflammation characterizing endometriosis. METHOD OF STUDY: This is a pilot study of mast cell numbers and its activation in endometriosis biopsies (n = 10) by immunostaining for mast cell tryptase, corticotropin-releasing hormone (CRH) and urocortin (Ucn). RESULTS: This is the first report that tryptase positive mast cells were not only increased (64-157 mast cells/mm(2)) in human endometriosis, but also highly activated (89%) in areas strongly stained positive for CRH/Ucn. Normal endometrium was weakly positive for both CRH/Ucn. CONCLUSION: High numbers of activated mast cells are present in endometriosis sites that were strongly positive for CRH/Ucn. CRH and Ucn may activate mast cells and contribute to the fibrosis and inflammation in endometriosis.     

Association study of corticotropin-releasing hormone receptor1 gene polymorphisms and antidepressant response in major depressive disorders

Hypothalamic-pituitary-adrenal (HPA) axis appears to play a key role in the pathogenesis of major depressive disorders (MDD). Treatment of certain selective serotonin reuptake inhibitors (SSRIs) has been shown to reduce the activity of corticotropin-releasing hormone (CRH) neurons and may contribute to their therapeutic action. It has been proposed that the downregulation of CRH activity is final and common step of antidepressant treatment. In this study, we tested whether the polymorphisms of three sites (rs1876828, rs242939 and rs242941) in corticotropin-releasing hormone receptor1 (CRHR1) gene are related to 6 weeks fluoxetine antidepressant effect in 127 Han Chinese patients with MDD. The results show that the rs242941 G/G genotype and homozygous GAG haplotype of the three single-nucleotide polymorphisms (SNPs) are associated with fluoxetine therapeutic response in MDD patients of high-anxiety (HA). The results support the idea that the CRHR1 gene is likely to be involved in the antidepressant response in MDD.     

Electro-acupuncture relieves visceral sensitivity and decreases hypothalamic corticotropin-releasing hormone levels in a rat model of irritable bowel syndrome

Previous studies into electro-acupuncture (EA) treatment of irritable bowel syndrome (IBS) have principally focused on the peripheral effects of EA in a rat model of IBS. It is not known whether EA exerts central effects in this rat model. We have examined the effects of EA on hypothalamic corticotropin-releasing hormone (CRH) levels in a rat model of IBS provoked by colorectal distension (CRD) and forelimb immobilization. EA was administered once daily to IBS model rats over a period of 7 d; untreated IBS rats and controls were also studied. The behavioral response to distension was rated according to the abdominal withdrawal reflex (AWR) score; hypothalamic CRH levels were measured by radioimmunoassay. We report that EA treatment significantly decreased visceral sensitivity to CRD in this rat model. In treated animals, EA also decreased hypothalamic CRH to control levels. Reduced hypothalamic CRH levels may mediate the beneficial effects of EA in this rat IBS model.     

Variability in the secretion of corticotropin-releasing hormone, adrenocorticotropic hormone and cortisol and understandability of the hypothalamic-pituitary-adrenal axis dynamics--a mathematical study based on clinical evidence

Samrat Chatterjee and J. Chattopadhyay Agricultural and Ecological Research Unit, Indian Statistical Institute, 203, B.T. Road, Kolkata 700 108, India Email: nbairagi{at}math.jdvu.ac.in Email: samrat_ct{at}rediffmail.com Corresponding auhor. Email: joydev{at}isical.ac.in Received on September 4, 2006. Revised on October 19, 2007. Accepted on December 13, 2007. In this article, we have developed a simple mathematical modelthat captures the vital mechanisms of the hypothalamic-pituitary-adrenal(HPA) axis self-regulatory activities. For this, a system ofthree-component non-linear delay differential equations hasbeen proposed and analysed to observe the ultradian and circadianvariabilities of the hormone secretion of the HPA axis in normalsubjects. Our analysis reveals that a feedback mechanism issufficient to show the ultradian variability of the hormonesecretion pattern but fails to show the circadian variability.A central nervous system-driven pulse generator coupled withthe primary feedback mechanism can exhibit the ultradian aswell as circadian variability in the hormone secretion of theHPA axis. The model can also predict different dynamics of thenormal HPA axis following physiological changes (viz. adrenalectomyand hypophysectomy) and pathological changes (viz. infusionof different hormones).     

Endocrinology: The effect of nafarelin on human plasma adrenocorticotrophic hormone and cortisol concentrations

This study assessed the effects on plasma adrenocorticotrophichormone (ACTH) and cortisol concentrations of 3 months' treatmentwith intranasal nafarelin 200 µg b.d. in 11 women (aged26–43 years) for the treatment of endometriosis (n = 9),fibroids (n = 1) and pre-menstrual syndrome (n = 1). Serialblood samples were taken over 5 h, before and after nafarelinadministration on the first day of treatment, and after 1 and3 months' treatment. Control samples were taken before and afterintranasal placebo administration on the day before nafarelinwas commenced. The area under the curve (AUC) for mean ACTHconcentrations at each time point from 0 to 240 min was calculated.There were no statistically significant changes in total secretionof either ACTH or cortisol. There was a transient rise in ACTH30–60 min after nafarelin administration on the firstday of treatment in seven out of 11 women. The rise did notexceed the normal range. Seven women with ovarian suppression(oestradiol concentration < 175 pmol/l by day 28) had consistentlylower mean ACTH concentrations at all time points than the fourremaining women who had oestradiol concentrations 222–880pmol/l by day 28. Cortisol concentrations were unaffected bynafarelin. We conclude from the results of this study that 3months' treatment with nafarelin has no effects on adrenal function,as assessed by ACTH and cortisol concentrations.     

Preliminary results on mood state, salivary testosterone:cortisol ratio and team performance in a professional soccer team

Mood, as measured by the profile of mood states questionnaire (POMS), salivary cortisol (F) and testosterone (T) levels, and performance were examined in 17 male soccer players 4 times during a season. Soccer players provided three saliva samples when getting up (resting values, 8 a.m.), before breakfast (11.30 a.m.), and between 4.00p.m. and 6.00 p.m. The initial measures were performed 1 day following the start of season training (T₁). They were then performed before and after a high-intensity training programme (T₂ and T₃, respectively) and 16 weeks after T₃ (T₄). Iceberg profiles of POMS were observed during T₁, T₂ and T₃, which coincided with successful performance. Subsequent decreased performance between T₃ and T₄ coincided with a decrease in vigor and an increase in tension and depression. Indeed, when the normal nycthemeral rhythm for F was observed (i.e. a decrease from morning until evening at all times; T₁–T₄), there was seemingly a non-statistical elevation of F on the morning of T₃, which only became statistically significant at 11.30 a.m. on T₃. In spite of a post-high-intensity training programme (T₃) increase in catabolism, the soccer players presented iceberg profiles together with a high percentage of winning. Our results could suggest that in team soccer, a decreased T:F ratio does not automatically lead to a decrease in team performance or a state of team overtraining. It appears that combined psychological and physiological changes during high-intensity training are primarily of interest when monitoring training stress in relation to performance. Electronic Publication     

The effects of cortisol on insulin sensitivity in muscle

Holmäng , A. & Björntorp , P. 1992. The effects of cortisol on insulin sensitivity in muscle. Acta Physiol Scand 144 , 425–431. Received 12 September 1 991 , accepted 20 November 1991. ISSN 0001–6722. Department of Medicine I and The Wallenberg Laboratory, Sahlgren's Hospital, University of C., teborg, Sweden The effects of cortisol on insulin sensitivity were examined in rats with the euglycaemic, hyperinsulinaemic clamp technique. Uptake of 2–deoxyglucose and incorporation of glucose into glycogen was followed in the white gastrocnemius, extensor digitorum longus, red gastrocnemius and soleus muscles as well as the liver (only glycogen synthesis). Maximal velocity and fractional velocity of the insulin-sensitive part of glycogen synthase (FV %) was measured in the muscles, as well as muscle fibre composition and capillary density. After 24 h exposure to cortisol, insulin sensitivity was diminished in the clamp measurements. This was paralleled by a decrease in glycogen synthesis in the most insulin-sensitive red gastrocnemius and Soleus muscles, but not in the white gastrocnemius or extensor digitorum longus muscles or the liver, and no effect was seen on 2–deoxyglucose uptake in muscles. FV % was markedly inhibited in all muscles. After 48 h exposure to cortisol, glycogen synthesis was markedly inhibited in all muscles, and 2–deoxyglucose uptake in all except the least insulin-sensitive muscle, WG. No changes in muscle morphology were found. These results suggest that the insulin resistance caused by cortisol is elicited in a stepwise manner, starting with an inhibition in the glycogen synthesis system in insulin-sensitive muscles, later including all muscles as well as 2–deoxyglucose uptake. This occurs without changes in morphology.     

The effect of physical therapy on beta-endorphin levels

Beta-endorphin (βE) is an important reliever of pain. Various stressors and certain modalities of physiotherapy are potent inducers of the release of endogenous βE to the blood stream. Most forms of exercise also increase blood βE level, especially when exercise intensity involves reaching the anaerobic threshold and is associated with the elevation of serum lactate level. Age, gender, and mental activity during exercise also may influence βE levels. Publications on the potential stimulating effect of manual therapy and massage on βE release are controversial. Sauna, mud bath, and thermal water increase βE levels through conveying heat to the tissues. The majority of the techniques for electrical stimulation have a similar effect, which is exerted both centrally and—to a lesser extent—peripherally. However, the parameters of electrotherapy have not yet been standardised. The efficacy of analgesia and the improvement of general well-being do not necessarily correlate with βE level. Although in addition to blood, increased brain and cerebrospinal fluid βE levels are also associated with pain, the majority of studies have concerned blood βE levels. In general, various modalities of physical therapy might influence endorphin levels in the serum or in the cerebrospinal fluid—this is usually manifested by elevation with potential mitigation of pain. However, a causal relationship between the elevation of blood, cerebrospinal fluid or brain βE levels and the onset of the analgesic action cannot be demonstrated with certainty.     

The effects of L-theanine, caffeine and their combination on cognition and mood

L-Theanine is an amino acid found naturally in tea. Despite the common consumption of L-theanine, predominantly in combination with caffeine in the form of tea, only one study to date has examined the cognitive effects of this substance alone, and none have examined its effects when combined with caffeine. The present randomised, placebo-controlled, double-blind, balanced crossover study investigated the acute cognitive and mood effects of L-theanine (250 mg), and caffeine (150 mg), in isolation and in combination. Salivary caffeine levels were co-monitored. L-Theanine increased 'headache' ratings and decreased correct serial seven subtractions. Caffeine led to faster digit vigilance reaction time, improved Rapid Visual Information Processing (RVIP) accuracy and attenuated increases in self-reported 'mental fatigue'. In addition to improving RVIP accuracy and 'mental fatigue' ratings, the combination also led to faster simple reaction time, faster numeric working memory reaction time and improved sentence verification accuracy. 'Headache' and 'tired' ratings were reduced and 'alert' ratings increased. There was also a significant positive caffeine x L-theanine interaction on delayed word recognition reaction time. These results suggest that beverages containing L-theanine and caffeine may have a different pharmacological profile to those containing caffeine alone.     

药物对吸烟者血浆β-内啡肽与皮质醇水平的影响

观察药物对吸烟者血浆β－内啡肽和皮质醇水平的变化,探讨它们之间的相互关系,应用放射免疫分析法进行检测,吸烟组的血浆皮质醇及β－内啡肽明显高于对照组;自然戒断烟后,戒烟组的血浆皮质醇明显升高,而血浆β－内啡肽明显降低;治疗后,吸烟组的血浆β－内啡肽和皮质醇达到平衡,用药物戒烟可能是通过改善内源性阿片肽及下丘脑－垂体－肾上腺轴的功能而达到戒烟的效果。     

Salivary cortisol, stress and mood in healthy older adults: the Zenith study

The aims of this study were to investigate the relationship between salivary cortisol, stress and mood and to look at the circadian rhythms of positive (PA) and negative (NA) mood in older adults. The participants were 41 healthy adults aged 55-69 years, recruited in Northern Ireland as part of the European Commission-funded Zenith project. Salivary cortisol samples were obtained twice a day (2.30 p.m. and 10.30 p.m.) for 7 consecutive days in conjunction with momentary measures of positive (PA) and negative mood (NA), using PANAS and a trait measure of perceived stress (Perceived Stress Scale). Salivary cortisol levels were measured using an enzyme-linked immunoassay kit. Higher perceived stress levels were associated with lower afternoon PA (r=-0.46, p=0.003) and higher afternoon (r=0.43, p=0.007) and evening (r=0.45, p=0.004) NA. Lower afternoon PA was correlated with higher evening cortisol concentrations (r=-0.47, p=0.002). Greater afternoon PA variability was associated with higher evening cortisol concentrations (r=0.38, p=0.015). A high intra-class correlation between cortisol and positive mood was found (r=0.67, p=0.009). Previously established rhythms for positive and negative mood were confirmed. Interestingly, there was no association between salivary cortisol levels and perceived stress in these healthy older adults. Further, more extensive research is required to better understand the apparent interplay between these variables and ageing.