Circadian Variation in Cortisol Reactivity to an Acute Stressor

To investigate the role of the circadian pacemaker in cortisol reactivity to a cold pressor challenge, 26 diurnally subjects participated in a constant‐routine protocol and were divided into two groups. Group 1 started immediately after a monitored sleep period at 09:00 h, while group 2 started 12 h later. After 2 h of adaptation, a cold pressor test was presented every 3 h. The cortisol response was assessed by means of saliva samples that were taken before and after the test. The pretest samples were considered to be base‐rate measures and base‐rate values as subtracted from post‐test values were considered as reactivity measures. Both measures showed distinct Time‐of‐Day variations (respectively: F_7,168 = 16.92, p < 0.001, ε = 0.383; and F_7,175 = 8.01, p < 0.001, ε = 0.523). These findings are interpreted as evidence for the existence of an endogenous circadian periodicity underlying the sensitivity of the hypothalamus–pituitary–adrenal (HPA)‐axis to acute stress.     

Circadian variation in cardiac autonomic activity: reactivity measurements to different types of stressors

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.     

Circadian Variation in Cardiac Autonomic Activity: Reactivity Measurements to Different Types of Stressors

The role of endogenous circadian rhythmicity in autonomic cardiac reactivity to different stressors was investigated. A constant routine protocol was used with repeated exposure to a dual task and a cold pressor test. The 29 subjects were randomly divided into two groups in order to manipulate prior wakefulness. Group 1 started at 09:00 h immediately after a monitored sleep period, whereas group 2 started 12 h later. Measures of interbeat intervals (IBI), respiratory sinus arrythmia (RSA, a measure of parasympathetic activity), pre-ejection period (PEP, a measure of sympathetic activity), as well as core body temperature (CBT) were recorded continuously. Multilevel regression analyses (across-subjects) revealed significant (mainly 24 h) sinusoidal circadian variation in the response to both stressors for IBI and RSA, but not for PEP. Individual 24 + 12 h cosine fits demonstrated a relatively large interindividual variation of the phases of the IBI and RSA rhythms, as compared to that of the CBT rhythm. Sinusoidal by group interactions were found for IBI and PEP, but not for RSA. These findings were interpreted as an indication for endogenous circadian and exogenous parasympathetic (vagal) modulation of cardiac reactivity, while sympathetic reactivity is relatively unaffected by the endogenous circadian drive and mainly influenced by exogenous factors.     

Rhythms in human bone marrow and blood cells

In 24h studies of bone marrow (BM), circadian stage-dependent variations were demonstrated in the proliferative activity of BM cells from subsets of 35 healthy diurnally active men. On an average, the percentage of total BM cells in deoxyribonucleic acid (DNA) synthesis phase was 188% greater at midday than at midnight (circadian rhythm: p = 0.018; acrophase or peak time of 13: 16h). Patients with malignant disease (n = 15) and a normal cortisol circadian rhythm showed higher fractions of BM cells in S-phase at midday. Colony-forming units--granulocyte/macrophage (CFU-GM), an indicator of myeloid progenitor cells, showed the same circadian variation as DNA S-phase (average range of change or ROC = 136%; circadian rhythm: p < 0.001; acrophase of 12:09h). Deoxyribonucleic acid S-phase and CFU-GM in BM both showed a circannual rhythm (p = 0.015 and 0.008) with an identical acrophase of August 12. The daily peak in BM glutathione content, a tripeptide involved in cellular defense against cytotoxic damage, preceded BM proliferative peaks by 4-5 h (ROC = 31-90%; circadian rhythm: p = 0.05; acrophase of 08:30h). Myeloid (ROC = 57%; circadian rhythm: p = 0.056; acrophase at 08:40h) and erythroid (ROC = 26%; circadian rhythm: p = 0.01; acrophase of 13:01h) precursor cells were positively correlated (r = 0.41; p < 0.001), indicating a circadian temporal relationship and equal influence on S-phase of total BM cells. Yield of positive selected CD34+ progenitor stem cells also showed significant circadian variation (ROC = 595%; circadian rhythm: p = 0.02; acrophase of 12:40h). Thus, the temporal synchrony in cell cycling renders BM cells more sensitive at specific times to hematopoietic growth factors and cell cycle-specific cytotoxic drugs. Moreover, proper timing of BM harvesting may improve progenitor cell yield. When using marker rhythms in the blood to allow for individualized timing of BM procedures, the times of low values in white blood corpuscles, neutrophils, and lymphocytes and high values in cortisol were predictive of the times of highest BM erythroid, myeloid, and total S-phase numbers occurring in the following 12 h.     

Changes in adrenal and testicular activity monitored by salivary sampling in males throughout marathon runs

Measurement of cortisol and testosterone in saliva samples provided by marathon runners at 6.4 km (4-mile) intervals has been used for monitoring acute changes in adrenal and testicular activity, and the changes compared with mean values in timed samples on five rest days. The collection of mixed whole saliva was well accepted; the missed sample rate in the 8 runners in the Cardiff marathon was less than 10%. On rest days, salivary cortisol and testosterone were within the normal male range and showed a circadian rhythm; mean values at 08.00 h (23.5 nmol L-1; 258 pmol L-1, p less than 0.001, p less than 0.001 respectively) were higher than at 22.00 h (2.8 nmol L-1; 130 pmol L-1). In samples collected at 09.00 h, immediately prior to the Cardiff marathon, cortisol (25.1 nmol L-1) and testosterone (304 pmol L-1) were higher than the mean values (14.9 nmol L-1; 209 pmol L-1) on non-run days. Concentrations of both steroids increased during the marathon; testosterone peaked (442 pmol L-1) at 21 miles, whereas cortisol continued to increase, being maximal (87.9 nmol L-1) at 30 min after completion of the run. Four of the runners in the Cardiff marathon also participated in the Bristol marathon and the changing patterns in salivary hormones were strictly comparable. Salivary sampling would appear to be of value in monitoring acute and rhythmic changes in endocrine function in marathon runners. The temporal relationship between changes in salivary cortisol and testosterone are consistent with direct inhibition of testicular secretion by high cortisol concentrations.     

Circadian phase difference of leptin in android versus gynoid obesity

A circadian rhythm in serum leptin, measured every 4 h for 24 h, characterizes normal-weight women (N = 14), and women with gynoid (N = 17) or android (N = 26) obesity, peaking around midnight (P < 0.05), but differing by about 3 h between android and gynoid women (P < 0.01). Obesity is associated with a higher MESOR (rhythm-adjusted mean; P < 0.001) and a smaller relative circadian amplitude (P < 0.05). Gynoid obesity is associated with a larger circadian amplitude of cortisol (P < 0.05), whereas android obesity is associated with a larger circadian amplitude and a higher MESOR of insulin (P < 0.05). Understanding putative mechanisms underlying different body fat distribution may lead to improved chronotherapeutic measures.     

Circadian variations in plasma renin activity, catecholamines and aldosterone during exercise in women

Four women were studied at 0400 h and 1600 h to determine if their hormonal and hemodynamic responses to exercise varied with the circadian cycle. Esophageal temperature was measured during rest and exercise (60% peak VO2; 30 min) in a warm room (Ta = 35 degrees C; PH2O = 1.7 kPa). Venous blood samples were drawn during rest and exercise and hemoglobin concentration (Hb), hematocrit (Hct), plasma osmolality (Posm), plasma protein concentration (Pp), colloid osmotic pressure (COP), plasma renin activity (PRA), cortisol, aldosterone, norepinephrine (NE) and epinephrine (E) were determined. Changes in plasma volume (PV) were estimated from changes in Hb and Hct. The relative hemoconcentration (-11.2%) was similar at 0400 h and 1600 h, but the absolute PV was smaller at 1600 h than at 0400 h (p = 0.03). The responses of Posm, Pp and COP to exercise were unaffected by time of day. Although PRA was not different at the two times of day, PRA was 244% greater during exercise at 1600 h, but only 103% greater during exercise at 0400 h. The normal circadian rhythms in plasma aldosterone (p = 0.043) and plasma cortisol (p = 0.004) were observed. Plasma aldosterone was 57% greater during exercise, while plasma cortisol did not change. The change in E and NE was greater at 0400 h, but this was due to the lower resting values of the catecholamines at 0400 h. These data indicate that time of day generally did not affect the hormonal or hemodynamic responses to exercise, with the exception that PRA was markedly higher during exercise at 1600 h compared to 0400 h.     

The effects of circadian rhythmicity of salivary cortisol and testosterone on maximal isometric force, maximal dynamic force, and power output

The study investigated the effects of circadian rhythm of cortisol (C) and testosterone (T) on maximal force production (Fpeak) and power output (Ppeak). Twenty male university students (mean age = 23.8 ± 3.6 years, height = 177.5 ± 6.4 cm, weight = 78.9 ± 11.2 kg) performed 4 time-of-day testing sessions consisting of countermovement jumps (CMJs), squat jumps (SJ), isometric midthigh pulls (IMTPs), and a 1-repetition maximum (1RM) squat. Saliva samples were collected at 0800, 1200, 1600, and 2000 hours to assess T and C levels on each testing day. Session rate-of-perceived exertion (RPE) scores were collected after each session. The results showed that Fpeak and Ppeak presented a clear circadian rhythm in CMJ and IMTP but not in SJ. One repetition maximum squat did not display a clear circadian rhythm. Session RPE scores collected at 0800 and 2000 hours were significantly (p ≤ 0.05) higher than those obtained at 1200 and 1600 hours. Salivary T and C displayed a clear circadian rhythm with highest values at 0800 hours and lowest at 2000 hours; however, no significant correlation was found between T and C with Fpeak and Ppeak. A very strong correlation was found between Taural with Fpeak of CMJ and IMTP and Ppeak of CMJ (r = 0.86, r = 0.84 and r = 0.8, p ≤ 0.001). The study showed the existence of a circadian rhythm in Fpeak and Ppeak in CMJ and IMTP. The evidence suggests that strength and power training or testing should be scheduled later during the day. The use of Taural seemed to be a more effective indicator of physical performance than hormonal measures, and the use of session RPE should also be closely monitored because it may present a circadian rhythm.     

Absence of apparent circadian rhythms of gonadotropins and free alpha-subunit in postmenopausal women: evidence for distinct regulation relative to other hormonal rhythms

Aging is associated with a decrease in gonadotropin levels in postmenopausal women (PMW) and is also associated with alterations in a number of circadian rhythms. The goals of this study were to determine the presence of circadian rhythms of gonadotropins and glycoprotein free alpha-subunit (FAS) in young and old PMW. Healthy, euthyroid PMW, ages 45 to 55 years (n = 11) and 70 to 80 years (n = 11), were admitted in the morning to start a 24-h constant routine of light, temperature, position, and activity. Subjects remained awake and semirecumbent for the duration of the study and were fed hourly snacks, and activity was monitored continuously. Blood was sampled every 5 min for two 8-h periods corresponding to the estimated acrophase and nadir of the temperature rhythm. Luteinizing hormone (LH) and FAS were measured in all samples and follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), and cortisol in 20-min serum pools. Mean LH (p < 0.001), FSH (p < 0.002), and FAS (p < 0.002) were lower in older compared with younger PMW. Day/night differences in cortisol and TSH (p < 0.001) were present in all subjects. However, there were no day/night differences in LH in younger or older PMW or in FSH in younger or older PMW. There were no day/night differences in mean FAS in younger or older PMW or in FAS pulse frequency or amplitude. Thus, in controlled studies in which differences in cortisol and TSH were demonstrated, there were no day/night differences in LH, FSH, or FAS in PMW. These studies suggest that despite evidence of intact circadian rhythms of cortisol and TSH, gonadotropin secretion does not appear to follow a circadian pattern in PMW. Thus, the age-related decline in gonadotropin secretion in PMW is not associated with a dampening of circadian rhythmicity. The absence of day/night differences in FAS suggests that GnRH plays a more prominent role in FAS regulation than does thyrotropin-releasing hormone in PMW.     

Lack of adult-type salivary cortisol circadian rhythm in hospitalized preterm infants

BACKGROUND/AIMS: Knowledge of the presence or absence of cortisol (F) circadian rhythm in preterm infants is important for the interpretation of F measurements made in samples taken for both clinical and research purposes. Little is known about its emergence in very preterm infants. This study examines circadian rhythm in F secretion in hospitalized infants born before 30 weeks' gestation. METHODS: Design: Prospective longitudinal observational study. Subjects: 11 infants admitted consecutively and born before 30 completed weeks of gestation. Measurements: F was measured by highly specific radioimmunoassay on morning and evening saliva samples gathered at weekly intervals until discharged home. Circadian rhythm was defined as > or =40% reduction from morning to evening level. RESULTS: For all data, the median salivary F was 10.3 nmol/l (range <0.5-372.8). F levels were highest in the first 3 weeks of life. No infants displayed classical circadian rhythm for 4 weeks or more prior to being discharged from hospital. The other infants showed randomly distributed morning and evening F values with a trend in 4 infants towards periods of consistently higher evening than morning values. CONCLUSION: Adult-type F circadian rhythm is rarely evident in hospitalized preterm infants born before 30 weeks' gestation.     

Mood and the circadian system: investigation of a circadian component in positive affect

The aim of this study was to test if the pattern of human mood variation across the day is consistent with the hypothesis that self-reports of positive affect (PA) have a circadian component, and self-reports of negative affect (NA) do not. Data were collected under two protocols: normal ambulatory conditions of activity and rest and during a 27 h constant routine (CR) procedure. Mood data were collected every 3 h during the wake span of the ambulatory protocol and hourly during the 27 h CR. In both protocols, rectal temperature data were continuously recorded. In the ambulatory protocol, activity data were also collected to enable estimation of the unmasked (purified) temperature rhythm. Participants were 14 healthy females aged 18-25 yr in the follicular phase of the menstrual cycle. Under both protocols, PA exhibited significant 24 h temporal variation [CR: F(23, 161) = 2.12, p < 0.01; ambulatory: F(5,55) = 2.44, p < 0.05] with a significant sinusoidal component [CR: F(2, 21) = 7.51, p < 0.01; ambulatory: F(2,3) = 20.49, p < .05] of the same form as the circadian temperature rhythm. In contrast, NA exhibited an increasing linear trend over time under the ambulatory protocol [F(1, 11) = 5.74, p < 0.05] but nonsignificant temporal variation under the CR protocol. The findings support the hypothesis of a circadian component in PA variation.     

Heart-rate reactivity to cold pressor stress following biofeedback training

Three previous studies have shown that biofeedback training is useful in modifying heart-rate and pain ratings during ice water stimulation (cold pressor test). Subjects were given an initial cold pressor followed by heart-rate biofeedback training and a final cold pressor test in which they were instructed to control their heart rate in accordance with the prior training. It was assumed that a heart-rate control skill had been learned. In the present study, two groups of subjects (N = 9 each) were given either increase or decrease heart-rate biofeedback training following the same procedures as previously, but subjects were not instructed to control their heart rate during the final cold pressor test. Heart rate, skin conductance, electromyographic activity, and respiration were measured. The biofeedback training effects replicate the previous results. However, no heart-rate or pain rating differences were found between the two groups during the final cold pressor test. Thus, previous findings cannot be accounted for simply by a shift in heart rate and/or pain reactivity following training itself. The findings suggest that a biofeedback strategy may be useful in modifying physiological and subjective responses to painful stimuli but only if it can be used as an active coping skill.     

Adrenocortical responsiveness to the synthetic ACTH 1-17 analogue given at different circadian stages

The study concerns the adrenocortical glucocorticoid responsiveness to the ACTH 1-17 analogue given at different times of the day, namely near to the zenith and the nadir of the circadian curve of plasma cortisol. Two schedules of administration of the heptadecapeptide have been performed: a pulse i.v. injection of 4 microgram; b. i.m. injection of 100 microgram. Both the doses were given to the same subject in the morning and in the evening of different days. The chrono-sensitivity of the adrenal cortex to ACTH 1.17 analogue is well evident after pulse stimulation by a micro-dose of the heptadecapeptide; in fact the plasma cortisol increase from basal values is significantly higher in evening than in the morning (p less than 0.001). The cortico-stimulatory effect of the higher dose of ACTH 1.17 analogue lasts about 12 h. and then plasma and urinary glucocorticoids take the usual circadian pattern again.     

Salivary cortisol increases after bariatric surgery in women

Cortisol increases have been associated with psychological and physiological stress; however, cortisol dynamics after weight loss (bariatric) surgery have not been defined. Obese participants not using exogenous glucocorticoids were eligible to participate. Female participants (n=24) provided salivary cortisol samples at bedtime, upon awakening the following morning, and 30?min after awakening before, and at 6 or 12 months after bariatric surgery. The Medical Outcomes Study Short Form-12 version 2 questionnaire regarding health-related quality of life was also completed. Preoperatively, mean body mass index was 45.1±8.1?kg/m2. Mean late night (1.8±1.1?nmol/l), awakening (10.7±7.4?nmol/l), and after-awakening (11.5±7.9?nmol/l) salivary cortisol values were within normal ranges. The cortisol awakening response (mean 21.1±79.7%, median 13.7%) was at the low end of normal. Preoperatively, participants had lower mental and physical health-related quality of life scores than US adult norms (p<0.001). Salivary cortisol was not correlated with measures of health-related quality of life. Mean BMI decreased over time (p<0.001) and participants experienced improved physical and mental health-related quality of life (p≤0.011). Postoperative late night salivary cortisol was not different from preoperative values. Awakening and after-awakening cortisol levels were higher than preoperative values (15.3±7.7?nmol/l, p=0.013; 17.5±10.2?nmol/l, p=0.005; respectively), but the cortisol awakening response was not changed (mean 26.7±66.2%; median 7.8%). Morning salivary cortisol increased at long-term follow-up after bariatric surgery. Although self-evaluated mental and physical health improved after surgery, the cortisol awakening response is at the low end of normal, which may indicate continued physiological stress.     

Differential β- and α-adrenergic activation during psychological stress

The responsivity of several cardiovascular indices to a computerized mental arithmetic stress and a cold pressor stress were investigated in 22 healthy adult subjects. The major findings were that the largely β-adrenergically driven T-wave amplitude, pre-ejection period, R-wave to pulse interval, and left ventricular ejection time values responded only to mental arithmetic; a significant decrease in cardiac output and increase in peripheral resistance were elicited during the cold pressor test; inter-beat-interval and subjective stress ratings responded significantly to both stresses compared to baseline levels, but more intensely to mental arithmetic than the cold pressor test; blood pressure, stroke volume and the maximum of the first derivative of the raw impedance signal responded unspecifically to both stresses. These findings support the idea that cardiovascular responses to psychological challenge depend on the level of cognitive processing required for the task. In addition, the superfluity of multiple variable measurements to study cardiovascular reactivity in such situations is discussed. Accepted: 3 September 1996     

Determination of whole body circadian phase in lung cancer patients: melatonin vs. cortisol

Background: A quantifiable and reliable technique for the determination of body circadian phase applicable to non-laboratory studies would allow the evaluation of circadian dysregulation. In this study we evaluated feasible methodologies to individualize whole body circadian phase in lung cancer patients. Methods: Cortisol and melatonin serum levels were measured in blood samples collected every 4 h for 24 h from eleven male controls and nine men suffering from non-small cell lung cancer. Circadian rhythmicity was evaluated and the 4-hourly fractional variations (FV) were calculated to evaluate the dynamics of the rise and fall in serum levels. Results: Overall cortisol serum levels were higher in cancer patients (p < 0.001), and lower for melatonin, but not significantly (p = 0.261). Original serum levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values at night for melatonin and near awakening for cortisol. Using all data after normalization to percent of individual mean, ANOVA detected a significant time-effect (p < 0.001) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) in each group. Overall fractional variation (FV) levels were lower for cortisol in cancer patients and higher for melatonin, but these differences were not significant. FV levels of cortisol and melatonin each showed a prominent 24 h oscillation in both study groups, with highest values prior to darkness onset for melatonin and near mid-dark for cortisol. ANOVA also detected a significant time-effect (p < 0.002) and cosinor analysis detected a significant 24 h rhythm (p < 0.001) for FV in each group, with maximal FV preceding maximal serum levels by ～3 h for melatonin and ～5 h for cortisol. Conclusions: A chronobiological evaluation of serum levels and fractional variations for cortisol and especially melatonin is a valuable methodology to define body circadian phase in lung cancer patients. It is possible to describe the complex process of hormone secretion with a methodology that allows the definition of both temporal characteristics and dynamic components. Impact: This kind of analysis might be useful in the study of hormone secretion(s) in cancer patients and other diseases and to guide therapeutic interventions. While lung cancer patients may have a negative prognostic value based upon stage and/or other hormonal aspects of their hypothalamus–pituitary–thyroid–adrenal axis function, patients that nevertheless maintain circadian rhythmicity in key body rhythm markers may still be eligible candidates for a chronotherapeutic approach of treatment(s).     

The within-pair resemblance in serum levels of androgens, sex-hormone binding globulin and cortisol in female obese identical twins - effect of negative energy balance induced by very low-calorie diet.

The first aim of the present study was to evaluate the changes in serum levels of cortisol, testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulphate (DHEA-S) and sex hormone-binding globulin (SHBG) in response to weight loss induced by one month of treatment with a very low-calorie diet (VLCD) in twelve pairs of female obese monozygotic twins. The second aim of the study was to investigate any within-pair resemblance in serum levels of steroids and SHBG before and after a negative balance protocol, as well as the resemblance in changes in response to therapeutic weight loss. VLCD-induced weight loss of 8.7+2.9 kg was associated with significant increases in serum testosterone (p<0.05) and SHBG (p<0.001) levels, whereas no significant changes in serum levels of cortisol, DHEA and DHEA-S were observed. Significant within-pair resemblances for both pre-treatment and post-treatment concentrations were revealed for DHEA-S (pre-treatment ICC = 0.795, p < 0.01, post-treatment ICC = 0.712, p < 0.01) and for testosterone (pre-treatment ICC = 0.594, p <0.05, post-treatment ICC = 0.735, p < 0.01). The baseline within-twin-pair resemblance in serum cortisol level at 7 a.m. (ICC=0.747, p < 0.05) was lost with VLCD treatment, while its concentration at 9 p.m. developed a within-pair similarity with weight loss (ICC = 0.824, p < 0.001). Similarly, VLCD treatment led to a significant within-pair resemblance in post-treatment level of DHEA (ICC = 0.755, p < 0.01), while no within-twin-pair resemblance was shown for either pre-treatment or post-treatment SHBG levels. None of the hormones measured exhibited any within-pair resemblance in response to VLCD-induced energy deficit, except for serum cortisol levels. A significant within-twin-pair resemblance in the changes in serum cortisol levels at 7 a. m. (ICC = 0.789, F = 8.5, p < 0.001), at 1 p.m. (ICC = 0.660, F = 4.9, p <0.01) and at 9 p.m. (ICC = 0.795, F = 8.8, p <0.001) were demonstrated even after adjustment for fat mass loss. An absence of any within-pair similarity was observed in both pretreatment and post-treatment levels of SHBG, while a significant within-pair resemblance in SHBG response to VLCD treatment (ICC = 0.658, p < 0.05) was recorded. We conclude that the significant within-twin-pair resemblance demonstrated for androgens and cortisol might suggest an important role for genetic factors in the regulation of their serum levels. Our results also suggest that the mechanisms controlling baseline levels of cortisol and SHBG differ from those influencing their responses to energy deficit induced by VLCD.     

The cortisol response to hypobaric hypoxia at rest and post-exercise

High altitude exposure normally leads to a marked natriuresis and diuresis. Acute mountain sickness is often associated with fluid retention, to which an elevated cortisol may contribute. Most investigators report a rise in resting cortisol with ascent, but little data exist regarding the cortisol response to a day trekking. We therefore measured salivary cortisol during ascent to > 5000 m in a cohort of between 42-45 subjects following a 6-h trek (samples taken between 15:30-16:30 h) and between 15-20 subjects at rest (morning samples taken between 08:00-09:00 h). Morning resting cortisol [nmol/l, mean±sd, (range)] was 5.5±2.9 (2.13-13.61) at 1300 m; 4.7±6.8 (1.4-27.02) at 3400 m, and significantly (p=0.002) rose between 4270 m [3.5±2.1 (1.4-8.34)] and 5150 m [14.5±30.3 (1.9-123.1)]. Post-exercise cortisol [nmol/l, mean±sd, (range)] dropped between 3400 m [7±6 (1.5-33.3)] and 4270 m [4.2±4.8 (1.4-29.5)] (p=0.001) followed by a significant rise in post-exercise cortisol between 4270 m [4.2±4.8 (1.4-29.5)] and 5 150 m [9.2±10.2 (1.4-61.3)] (p<0.001). There were no significant associations between severity of acute mountain sickness and cortisol levels. There was a significant though weak correlation between cortisol post-exercise at 5150 m and oxygen saturation at 5150 m (rho= - 0.451, p=0.004). In conclusion, this is the largest cohort to have their resting and post-exercise cortisol levels ascertained at high altitude. We confirm the previous findings of an elevated resting morning cortisol at > 5000 m, but present the novel finding that the cortisol response to a day trekking at HA appears suppressed at 4270 m.     

Effects of adrenocorticotropin stimulation on cortisol dynamics of pregnant gilts and their fetuses: implications for prenatal stress studies

The effect of adrenocorticotropic hormone (ACTH) administration on plasma cortisol concentrations was determined in pregnant gilts and their fetuses. In a first experiment, 100 IU ACTH (Synacthen Depot) was administered intramuscularly to the gilts every second day from Days 49 to 75 of gestation. ACTH injections were carried out at 08:00 h and, thereafter, 10 blood samples were taken within the following 8h via jugular catheters. Blood samples were analysed for plasma cortisol concentrations, and results were compared with values from animals which were treated with physiological saline and untreated animals (blood sampling only). The values for plasma cortisol concentrations increased until 3h after ACTH applications to a mean maximum level of 276.5+/-17.2 nmol/l in the whole 4-week stimulation period. Plasma cortisol levels did not return to pre-treatment values within the 8 h post-injection. No differences in cortisol levels were found between the physiological saline and untreated control, and no habituation of the adrenocortical response to ACTH was found during the 4-week stimulation period. In a second experiment, 100 IU ACTH were administered to pregnant gilts at gestation Day 65. After 3 h, fetuses were recovered under general anaesthesia and blood samples were taken from the umbilical vein, artery, and, after decapitation, from periphery. Application of ACTH to the sows significantly increased their plasma cortisol concentrations (P<0.001), and also increased plasma cortisol concentrations in peripheral blood samples from the fetuses (P=0.09) and in the umbilical vein (P<0.001) and artery (P<0.01), respectively. Plasma ACTH concentrations did not differ in fetuses from ACTH-treated or control sows. The results show that in gilts the adrenocortical response to an exogenous application of Synacthen Depot is consistent over time during mid-gestation. Furthermore, cortisol but not ACTH levels were increased in fetuses from ACTH-treated sows, indicating that maternal cortisol can cross the placenta during mid-gestation. The stimulation of maternal cortisol release through exogenous ACTH with subsequent elevation of fetal cortisol levels is, therefore, a useful approach for studying effects of elevated maternal glucocorticoids in prenatal stress studies in pigs.     

Plasma cortisol in cattle: Circadian rhythm and exposure to a simulated high altitude of 5,000 m

After a 2 week control period at 400 m, cattle were exposed to 5,000 m simulated altitude for 2 weeks, which was followed by a 2-week post-altitude control period. Plasma cortisol values from blood samples taken every 30 min for a total of 24 h indicated that cortisol was secreted episodically and that a circadian rhythm existed. When cortisol values were grouped into 4, 6-h periods, plasma cortisol was most abundant from 06:00 to 12:00 h with an average of 0.96µ g/100 ml and least abundant from 00:30 to 06:00 h with an average of 0.55µ g/100 ml. Plasma cortisol increased from 0.42 to 3.08µ g/100 ml during the 4 h ascent to 5,000 m and decreased to near normal levels the following day. A rhythmic plasma cortisol pattern was maintained after one day at simulated high altitude.