Glucocorticoid response to exercise as measured by serum and salivary cortisol

Serum and salivary cortisol concentrations were studied in 78 elite athletes engaged in different sports, by subjecting them to high-intensity laboratory exercise. The mean difference in the pre-exercise cortisol concentrations in the seven groups studied were more marked in serum (from 311 to 768 nmol.l-1) than in saliva (from 17.9 to 22.7 nmol.l-1, only one group reaching 40 nmol.l-1). Judging from the correlation coefficients based on total variances, the post-/pre-exercise differences in cortisol concentrations in serum depended chiefly on pre-exercise values, while those in saliva tended to depend more on the postexercise concentrations. The coefficients of correlation between that difference and either the pre- or postexercise values were -0.71 and 0.47, respectively, for serum, and -0.51 and 0.58, respectively, for saliva. This would suggest that salivary cortisol concentration might be a more suitable variable for assessing glucocorticoid activity in exercise than serum cortisol concentration, probably being less sensitive to pre-exercise emotional state.     

The salivary testosterone and cortisol response to three loading schemes

This aim of this study was to examine the free hormone (in saliva) responses to squat workouts performed by recreationally weight-trained males, using either a power (8 sets of 6 reps, 45% 1 repetition maximum [1RM], 3-minute rest periods, ballistic movements), hypertrophy (10 sets of 10 reps, 75% 1RM, 2-minute rest periods, controlled movements), or maximal strength scheme (6 sets of 4 reps, 88% 1RM, 4-minute rest periods, explosive intent). To determine the relative importance of the different training variables, these schemes were equated by workout duration with the power and strength schemes also equated by load volume. Salivary testosterone (T) and cortisol (C) both increased following the hypertrophy scheme (P < 0.05), with little to no hormonal change across the power and maximal strength schemes (P > 0.05). In general, the postexercise T and C responses to the hypertrophy scheme exceeded the other two schemes (P < 0.05). The greater volume of load lifted in the hypertrophy protocol over the same workout duration may explain the endocrine differences observed. The similar T and C responses to the power and maximal strength schemes (of equal volume) support such a view and suggest that differences in load intensity, rest periods, and technique are secondary to volume. Because the acute hormonal responses to resistance exercise contribute to protein metabolism, then load volume may be the most important workout variable activating the endocrine system and stimulating muscle growth.     

Salivary alpha amylase and salivary cortisol response to fluid consumption in exercising athletes

The objective of the study was to examine salivary biomarker response to fluid consumption in exercising athletes. Exercise induces stress on the body and salivary alpha amylase (sAA) and salivary cortisol are useful biomarkers for activity in the sympathoadrenal medullary system and the hypothalamic pituitary adrenal axis which are involved in the stress response. Fifteen college students were given 150 ml and 500 ml of water on different days and blinded to fluid condition. The exercise protocol was identical for both fluid conditions using absolute exercise intensities ranging from moderate to high. Saliva was collected prior to exercise, post moderate and post high intensities and analyzed by Salimetrics assays. Exercise was significant for sAA with values different between pre-exercise (85 ± 10 U · ml⁻¹) and high intensity (284 ± 30 U · ml⁻¹) as well as between moderate intensity (204 ± 32 U · ml⁻¹) and high intensity. There was no difference in sAA values between fluid conditions at either intensity. Exercise intensity and fluid condition were each significant for cortisol. Cortisol values were different between pre-exercise (0.30 ± 0.03 ug · dL⁻¹) and high intensity (0.45 ± 0.05 ug · dL⁻¹) as well as between moderate intensity (0.33 ± 0.04 ug · dL⁻¹) and high intensity. Moderate exercise intensity cortisol was lower in the 500 ml condition (0.33 ± 0.03 ug · dL⁻¹) compared with the 150 ml condition (0.38 ± 0.03 ug · dL⁻¹). This altered physiological response due to fluid consumption could influence sport performance and should be considered. In addition, future sport and exercise studies should control for fluid consumption.     

The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm.

Recent studies have shown that cortisol levels rapidly increase within the first 30 minutes after awakening. This response is rather robust over weeks or months and is altered by chronic stress and burnout. The present study investigated to what extent the cortisol response to awakening relates to responses following hCRH, ACTH(1-24), or psychosocial stress challenges in 22 healthy subjects. Furthermore, a 12-hour circadian cortisol profile was obtained to compare the morning response with cortisol levels obtained throughout the day. Results show that the morning cortisol response was of similar magnitude to that following injection of 1 microg/kg h-CRH or exposure to a brief psychosocial stressor (TSST). All of these were significantly smaller compared to maximal stimulation of the adrenal cortex by ACTH(1-24). Correlation analyses revealed that the morning cortisol response was closely related only to the cortisol response following 0.25 mg ACTH(1-24) (r=0.63, p=0.002). We conclude that the morning cortisol response to awakening can provide important information on the (re)activity of the HPA axis in addition to more 'traditional' methods like hCRH or Synacthen challenge tests. The sensitivity/capacity of the adrenal cortex appears to play a crucial role for the magnitude of cortisol responses observed after awakening.     

Increased ratio of serum cortisol to cortisone in acute-phase response

BACKGROUND/OBJECTIVES: 11beta-Hydroxysteroid dehydrogenase (11beta-HSD) enzymes convert cortisol into inactive cortisone and vice versa. While 11beta-HSD type 2 (mainly localized in the kidney) unidirectionally inactivates cortisol to cortisone, type I isoform (mainly localized in the liver) acts bidirectionally and can thus potentially restore cortisone to active cortisol. The aim of this pilot study was to investigate whether the serum cortisol:cortisone ratio is altered during the acute-phase response, possibly due to altered modulation of 11beta-hydroxysteroid dehydrogenase isoforms. METHODS: Using liquid chromatography electrospray tandem mass spectrometry, cortisol and cortisone were measured in the serum of hospitalized patients with normal and abnormal CRP concentrations, the latter indicating acute-phase response. Fifteen unselected samples were analyzed, all with a CRP concentration within one of the following ranges to cover a wide range of CRP concentrations evenly: <5, 5-20, 21-50, 51-100, 101-200, and >200 mg/l. RESULTS: In the heterogeneous study population, increased CRP concentrations significantly correlated with an increased cortisol:cortisone ratio (p < 0.001; r = 0.65, Spearman correlation coefficient). This correlation was independent of increased serum cortisol concentrations found by multivariate regression analysis. The median ratio was 6.4 (interquartile range 5.5-7.4; n = 30) in patients with a CRP concentration < or =20 mg/l, and 11.2 (interquartile range 8.8-13.9; n = 60) in patients with CRP >20 mg/l (p < 0.01). CONCLUSION: The balance between serum cortisol and cortisone is altered during acute-phase response with a shift towards active cortisol, suggesting that 11beta-HSD isoenzymes play a role in the modulation of systemically available cortisol during acute illness.     

Enhanced serum cortisol response to 5-hydroxytryptophan in depression and mania

The serum cortisol responses to D, L-5-hydroxytryptophan (5-HTP), 200 mg per oral, in unmedicated depressed and manic patients, were both significantly greater than that of normal controls. The cortisol response to 5-HTP in depressed patients was significantly correlated with ratings of specific symptoms of depression. It was also greater in non-psychotic than in psychotic depressed patients as well as in those manic or depressed patients who attempted suicide compared to those who had not. In view of evidence for decreased brain serotonergic activity in depression and perhaps mania, the results suggest at least some serotonin receptors may be supersensitive in some patients with affective disorders.     

Inbreeding as measured by isonymy in two Venezuelan populations and its relationship to other variables

Isonymy is a useful approach to the study of population structure and thus can be utilized to detect deviations from random mating. In this study we give the results of an analysis of inbreeding levels and relate such variables as mean marital distance, surnames repeated in isonymous couples, and percentage of people using only maternal surnames to inbreeding and endogamy in two Venezuelan populations of black ancestry, Birongo and La Sabana. These populations differ in their sociocultural development and degree of isolation. We estimated inbreeding through isonymy and directly from genealogy. The most important findings are that the Ft values are higher than the a's, that the Fn component of Ft is higher than the Fr component, and that there is higher endogamy, inbreeding, and isolation in Birongo than in La Sabana. These results are in agreement with the sociocultural and historical background and development of each population. Nevertheless, both populations show similar temporal trends in almost all the variables analyzed. The use of isonymy as a complementary tool to study population structure is proposed, especially for Ibero-American populations.     

Relationship of DNA ploidy to chemoresistance of tumors as measured by in vitro tests

To examine whether patients with aneuploid tumors might derive more benefit from chemotherapy than would patients with diploid tumors, predictive tests for determining resistance in human tumors were carried out and the test results compared with the DNA ploidy of the corresponding tumors. Multidrug-resistance in 15 kidney carcinomas grown as primary cultures was determined by immunofluorescence by Mab C219, which is specific for the plasma membrane glyco-protein P-170, and by the use of tritiated nucleotide incorporation after addition of doxorubicin. Aneuploid tumors had a higher tendency to be more sensitive than diploid tumors, but the correlation was not significant. This was confirmed by reanalyzing our earlier data on ovarian and lung cancers. In conclusion, DNA measurement using flow cytometry does not appear to be a suitable tool for prediction of resistance of human tumors to chemotherapy.     

The role of salivary cortisol and DHEA-S in response to sexual, humorous, and anxiety-inducing stimuli

Stress and anxiety are commonly thought to be detrimental to sexual function. Several studies in both the human and animal literature, however, have found that inducing anxiety can enhance sexual function in women. The mechanisms that explain a negative relationship between physical and psychological stress and sexual functioning are well documented, but little is known about how stress or anxiety might have a facilitatory effect on sexual arousal. As an initial step in exploring the relationship between anxiety and sexual arousal, the present study examined the role of the autonomic nervous system, and the adrenal hormones cortisol and dehydroepiandrosterone-sulfate (DHEA-S) in response to a sexual film, an anxiety-inducing film, and a humorous film. Nineteen premenopausal women (mean age 24.4 years) who were free from sexual difficulties came into the lab on three separate days. At each session they were shown an anxiety-inducing, sexually arousing, or humorous (control) film while their physiological arousal was measured. They also provided saliva samples before and after each film. Cortisol significantly decreased, while DHEA-S increased in the sexual and humorous conditions. Neither hormone changed significantly in the anxiety-inducing condition. Autonomic nervous system activity measured by heart rate and heart rate variability did not change in response to the sexual or anxiety-inducing films, but heart rate variability increased significantly in response to the humorous film. The cortisol/DHEA-S ratio at the post-sexual film time point was significantly negatively correlated with genital arousal (measured by vaginal pulse amplitude). Anxiety-inducing films did not result in a physiological stress response, which can explain why they do not impair sexual function.     

Serum cortisol radioimmunoassay values in the normal ferret and response to ACTH stimulation and dexamethasone suppression tests

Cortisol values were obtained from 39 ferrets, Mustela putorius furo, by using a commercial radioimmunoassay. Sera from 25 males (18 intact, 7 neutered) and 14 females (7 intact, 7 spayed) were assayed. Resting serum cortisol values ranged from 0.13 to 2.70 micrograms/dl for males (mean = 0.93 +/- 0.63 micrograms/dl), and 0.55 to 1.84 micrograms/dl for females (mean = 0.86 +/- 0.29 microgram/dl). The resting cortisol values of both males and females were comparable to those of the cat (1.0 to 3.0 micrograms/dl). A 7 year old male ferret with suspected hyperadrenocorticism and an adrenal mass had a cortisol level of 8.1 micrograms/dl. Adrenal cortical carcinoma was the histologic diagnosis. One adult female ferret had a cortisol level of 3.30 micrograms/dl. This animal also had proliferative colitis upon necropsy. An ACTH stimulation test (1 U/kg IM) and a low-dose dexamethasone suppression test (0.1 mg/kg) were performed on 10 ferrets. Post-ACTH serum cortisol levels increased by an average of 89%. Post-dexamethasone serum cortisol values decreased by an average of 18% 6 hours post-injection.     

High correlation between salivary cortisol awakening response and the psychometric profiles of healthy children

Background

Cortisol awakening response (CAR) as an indicator of psychological stress and related physical and psychiatric diseases has attracted growing attention from researchers. Although CAR changes have been investigated extensively in children with behavioral and psychiatric disorders, the association between CAR and conventional psychometric scales for healthy children has not been reported. The aim of this study was to investigate the association between salivary CAR and subscales of Profiles of Mood States (POMS), a self-assessment questionnaire widely used to evaluate the temporal emotional states of healthy children.

Findings

This study included 18 healthy girls aged 13–16 years. Saliva was collected immediately on awakening, 30 min and 60 min after waking, and then at 2-hour intervals from 9 am to 5 pm. The current mood state, including depression, anxiety, fatigue, and other psychometric profiles were assessed using POMS. The magnitude of salivary CAR and the area under the concentration-time curve (AUC) for diurnal salivary cortisol were compared with the profiles. There were significant positive correlations between the magnitude of CAR and the POMS subscales for "Depression-Dejection", "Tension-Anxiety", "Fatigue", and "Confusion". No correlation was found between the AUC salivary cortisol level and the psychometric profiles.

Conclusions

Salivary CAR was associated with various mood states of healthy female children but diurnal salivary cortisol AUC was not. Salivary CAR may be a biomarker of the physical and mental condition of healthy female children.

     

Low heritability and high phenotypic plasticity of salivary cortisol in response to environmental heterogeneity in a wild pinniped

Individuals are unique in how they interact with and respond to their environment. Correspondingly, unpredictable challenges or environmental stressors often produce an individualized response of the hypothalamic‐pituitary‐adrenal (HPA) axis and its downstream effector cortisol. We used a fully crossed, repeated measures design to investigate the factors shaping individual variation in baseline cortisol in Antarctic fur seal pups and their mothers. Saliva samples were collected from focal individuals at two breeding colonies, one with low and the other with high density, during two consecutive years of contrasting food availability. Mothers and pups were sampled concurrently at birth and shortly before weaning, while pups were additionally sampled every 20 days. We found that heritability was low for baseline cortisol, while within‐individual repeatability and among‐individual variability were high. A substantial proportion of the variation in baseline cortisol could be explained in pups and mothers by a combination of intrinsic and extrinsic factors including sex, weight, day, season, and colony of birth. Our findings provide detailed insights into the individualization of endocrine phenotypes and their genetic and environmental drivers in a wild pinniped. Furthermore, the strong associations between cortisol and life history traits that we report in fur seals could have important implications for understanding the population dynamics of species impacted by environmental change.     

A laboratory exercise to illustrate increased salivary cortisol in response to three stressful conditions using competitive ELISA

Perceived stress activates the hypothalamus-pituitary-adrenal axis, resulting in the release of glucocorticoids into the systemic circulation. Glucocorticoids cause the elevation of blood glucose, providing the necessary energy for the organism to cope with stress. Here, we outline a laboratory exercise that uses a competitive ELISA kit to illustrate the response of salivary cortisol concentrations to three stressful conditions. Twelve undergraduate students in the General and Comparative Endocrinology course at Iowa State University were subjected to presentation stress, fasting stress, and competition stress to determine their effect on salivary cortisol concentrations. Students had elevated salivary cortisol in response to each of these stresses compared with basal conditions. These results reiterate the importance of glucocorticoids as mediators of the stress response. This study also incorporates the use of the ELISA technique, a modern laboratory tool used to determine the amount of endogenous antigens in plasma or saliva. This laboratory exercise can easily be adapted to fit into already existing physiology and endocrinology curriculums.     

Pain modulation by adrenergic agents and morphine as measured by three pain tests

The effects of several adrenergic agents on pain and morphine analgesia were assessed using three pain tests in rats. These tests--Tail-Flick, Hot-Plate, and Formalin--allow comparison of the effects of different noxious stimuli and different motor responses. Each pain test yielded a unique constellation of adrenergic influences, suggesting that variation of stimulus and response parameters can change the functional expression of adrenergic systems related to pain processing. The salient drug effects include: 1) a pronounced, relatively selective analgesic effect of yohimbine in the Hot-Plate test; 2) a selective analgesic effect of clonidine in the Formalin test; 3) a strikiny, but variable, antagonism of morphine analgesia by a combination of yohimbine and propranolol in the Formalin test; 4) a nonlinear dose-response curve for antagonism of morphine analgesia by propranolol in the Hot-Plate test; and 5) a generalized interference with pain responding and enhancement of morphine analgesia by most drrgs in the Formalin test. The data suggest that the type of pain test is crucial in determining the pattern of drug influences that is revealed.     

The serum cortisol:cortisone ratio in the postoperative acute-phase response

OBJECTIVE: In a previous cross-sectional pilot investigation, an increase in the ratio of active cortisol to inactive cortisone in serum has been found as a general phenomenon during the acute-phase response. The aim of the present study was to further characterize this alteration of cortisol metabolism in patients undergoing elective cardiac bypass surgery. METHODS: Cortisol and cortisone were quantified by use of liquid-chromatography tandem mass spectrometry in sera that were sampled preoperatively and on the first 4 postoperative days (POD) from 16 patients undergoing aortocoronary bypass grafting (7.00 a.m.). RESULTS: The median serum cortisol concentration peaked on the first POD and then decreased statistically significantly until the end of the observation period: preoperatively, 245 nmol/l (IQR 198-331); 1st POD, 532 nmol/l (IQR 409-678 ); 4th POD, 373 nmol/l (IQR 306-493); p for trend = 0.019. In contrast, the cortisol:cortisone ratio was constantly increased approximately twofold on all POD compared to preoperative sampling: preoperatively, 5.4 (IQR 5.0-7.2); 1st POD, 11.3 (IQR 9.2-13.6); 4th POD, 9.9 (IQR 7.7-11.0), with no significant trend of normalization. CONCLUSION: Following major surgery, the substantial increase in the serum cortisol:cortisone ratio - reflecting a shift in the overall set-point of 11beta-hydroxysteroid dehydrogenase activity - is more sustained than the increase in serum cortisol; the increase in the cortisol:cortisone ratio seems to be a long-term phenomenon of the activation of the hypothalamic-pituitary-adrenocortical system by surgical stress and systemic inflammation.     

Prolactin response to TRH is unaltered by pulsatile infusion of LHRH

Eleven boys with constitutional delay of puberty and 7 patients with hypogonadotrophic hypogonadism underwent standard thyrotrophin-releasing hormone (TRH) tests prior to and following 6 days' pulsatile infusion of luteinizing hormone-releasing hormone (240 ng/kg/pulse). There were no significant differences in basal, peak or incremental prolactin responses to TRH between the 2 groups of patients and there were no differences in the magnitude of prolactin response to TRH in either group of patients during pulsatile therapy when compared with preinfusion responses.     

Stress and abdominal fat: preliminary evidence of moderation by the cortisol awakening response in Hispanic peripubertal girls

Stress and the cortisol awakening response (CAR) have been independently linked to increases in abdominal fat depots. This cross-sectional study examined the CAR as a moderator of the association between stress, visceral adipose tissue (VAT), and subcutaneous abdominal adipose tissue (SAT) in a sample (N = 23) of female peripubertal Hispanic girls aged from 8 to 11. The study included: (i) monitored salivary cortisol collection, (ii) VAT and SAT obtained by multislice magnetic resonance imaging, and (iii) a stressful life events checklist with four domain-specific subscales: peer, family, personal, and school. Regression analysis indicated an interaction of school-related life events and CAR on VAT and SAT, with greater numbers of school-related events being related to greater VAT and SAT for girls with high CAR, but no association with VAT or SAT for girls with low CAR. Similar to job stress in adults, school-related stress in children may contribute to central adiposity, especially for girls with high CAR.     

Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity

Adrenocortical activity can be assessed by measurement of free cortisol in saliva. Cortisol status has important health implications in both physical and psychological terms. Assessment of cortisol status is complicated by the marked diurnal cortisol cycle. This cycle is characterised by an increase in secretory activity following awakening to achieve the morning acrophase. Thereafter it falls with a declining trend over the remainder of the day. For between subject studies the timing of sampling in relation to this cycle is an important consideration. We report a comprehensive study of the diurnal free cortisol cycle designed to analyse its components and to investigate their reliability and inter-relatedness. We instructed 42 healthy volunteers to collect saliva samples at home on two consecutive days. On each day the first sample was collected immediately upon awakening, followed by a further three samples at 15-minute intervals which collectively comprised the "awakening samples". A further four sample's were collected through the day at 3-hour intervals, all synchronized to awakening time. The cortisol response to awakening was calculated in two ways. Overall cortisol production in the first 45 minutes after awakening was calculated as area under the cortisol curve with reference to zero (AUC). The dynamic of the cortisol response to awakening was calculated as area under the cortisol response curve (AURC) with reference to the first awakening sample. In addition the underlying cortisol secretory activity was assessed based upon the diurnal three-hourly samples. All three parameters of adrenocortical activity showed reasonable stability across the two sampling days indicating all were reliable indexes of trait characteristic. AUC was representative of underlying diurnal activity but AURC was not. Measurement at any time point, 3, 6, 9 or 12 hours post-awakening was representative of the underlying 12-hour diurnal activity.     

Diagnostic performance of salivary cortisol and serum osteocalcin measurements in patients with overt and subclinical Cushing's syndrome

ObjectiveThe cut-off value for salivary cortisol measurement for the diagnosis of Cushing's syndrome (CS) may depend both on the severity of the disease and the composition of control group. Therefore, we examined the utility of midnight salivary cortisol measurements in patients who were evaluated for signs and symptoms of CS or because they had adrenal incidentalomas. Because serum osteocalcin (OC) is considered as a sensitive marker of hypercortisolism, we also investigated whether OC could have a role in the diagnosis of CS.Patients and methodsEach of the 151 patients was included into one of the following groups: (A) overt CS (n = 23), (B) subclinical CS (n = 18), (C) inactive adrenal adenomas (n = 40), (D) patients without HPA disturbances (n = 70). Patients (C + D) were used as controls. Serum, salivary and urinary cortisol, and OC were measured by electrochemiluminescence immunoassay.ResultsGroup A had suppressed OC as compared to both group B and group (C + D). Serum and salivary cortisol concentrations showed strong negative correlations with OC in patients with overt CS. The areas under the curves of salivary and serum cortisol at 24:00 h (0.9790 and 0.9940, respectively) serum cortisol after low dose dexamethasone test (0.9930) and OC (0.9220) obtained from ROC aanalysis for the diagnosis of overt CS were not statistically different.ConclusionThis study confirms the usefulness of midnight salivary cortisol measurements in the diagnosis of overt CS in the everyday endocrinological praxis. Our results suggest that OC may have a role in the diagnosis of overt CS.