The purpose of this study was to investigate endocrine responses to redistribution with heavier loads (RR+L) during back squat (BS) exercise in resistance-trained men. Ten men (mean±SE; 23±2 years, 175.6±2.0 cm, 78.0±3.4 kg, 4±1 training years) were assigned using randomization to either RR+L (4 sets of (2×5 repetitions) of BS with 30 s intra-set and 90 s inter-set rest using 75% of their 1RM) or traditional sets (TS; 4 sets of 10 repetitions of BS with 120 s inter-set rest using 70% of their 1RM). Fasted blood samples were collected pre-exercise (PRE), immediately post-exercise (IP), and 5 (+5), 15 (+15), and 30 (+30) minutes post-exercise to analyze the concentrations of testosterone (T), growth hormone (GH), cortisol (C), and blood lactate (BL). Two-way ANOVAs with repeated measures were used (p≤0.05). A main effect of condition (p=0.023) was observed for BL (RR+L; 5.9±0.5 vs TS; 6.7±0.4 mmol/L). A main effect of time point (p≤0.001) was observed for T, GH, C, and BL. T was greater at IP (8.8±1.1), +5 (9.0±1.1), +15 (8.5±1.0), and +30 (8.0±1.0) than PRE (7.1±0.8 ng/mL). GH was greater at IP (58.3±12.7), +5 (62.8±12.7), +15 (67.9±13.3), and +30 (52.8±11.2) than PRE (3.6±1.6 µIU/mL). C was greater at +15 (25.5±2.9) and +30 (25.6±2.7) than PRE (20.0±2.7 µg/dL). BL was greater at IP (8.6±0.6), +5 (8.2±0.6), +15 (7.4±0.5), and +30 (5.8±0.5) than PRE (1.4±0.2 mmol/L). RR+L resulted in lower BL but no differences in T, GH, and C responses compared to TS. Thus, practitioners may incorporate RR+L without affecting endocrine responses.

Le travail de cette thèse s’inscrit dans le cadre du projet ANR SUSoSTRESS qui a pour objectif la compréhension des mécanismes moléculaireset génétiques sous-jacents à la variabilité individuelle de réponses de stress et a collecté des données longitudinales à plusieurs niveaux biologiquessur une population d’étude porcine (race Large White). La thèse est organisé en deux partie. La première partie s’articule autour de l’analyse de données cliniques et transcriptomiques collectées à plusieurs pas de temps avant et après application de deux types de stress : injection d’ACTH et de LPS. Dans cettepartie, on cherche à développer d’un modèle fonctionnel permettant de décrire et d’intégrer au mieux l’ensemble des sources de variation génétique du fonctionnement de l’axe corticotrope et plus généralement des réponses de stress dans notre population d’étude. Plus précisément, il s’agit d’élaborer un modèle (au sens biologique du terme) décrivant les différentes réponses biologiques de stress et l’influence des variations génétiques (simples et en interaction), dans le but de prédire les leviers les plus efficaces en fonction de l’objectif de sélection. Ce travail a mis en évidence une liste de 65 gènes différentiellement exprimé au cours des réponses au stress, dont un ensemble de 8 gènes liés au au cortisol (l’hormone principale du stress) par NR3C1, le récepteur aux glucocorticoides. Ces gènes sont des biomarqueurs potentiels pouvant être fournis aux éleveurs en tant que leviers de sélection permettant un meilleur équilibre entre amélioration des caractères de production et des caractères de robustesse. La deuxième partie de ce travail s’articule autour du développement d’un outil d’analyse statistiques adapté à l’intégration de données ’omiques longitudinalesavec une variable cible d’intérêt.Nous proposons la «multiway-SIR », qui étend la méthode dual-STATIS, une méthode d’analyse de données cubiques non supervisée, au cadre de la SIR, une méthode de régression semi-paramétrique pouvant être utilisée à des fins exploratoires. Cette méthode est appliquée sur les données cliniques de l’expérience d’ACTHet permet d’y explorer l’influence de la variabilité de la réponse du cortisol à une injection d’ACTH.

Delirium, or “acute confusion” is a common and serious acute neuropsychiatric syndrome mainly affecting older people. It is associated with multiple adverse outcomes, including an increased risk of developing dementia and increased mortality. The underlying mechanisms of delirium are poorly understood, and there are currently no specific treatments. This thesis investigated the roles of the hypothalamic-pituitary adrenal axis and inflammation in the pathophysiology of delirium, persistent delirium and cognitive decline following delirium. It investigated whether levels of cortisol in blood and cerebrospinal fluid (CSF) are elevated in delirium, with elevated pro-inflammatory and reduced anti-inflammatory cytokines. It also investigated whether there is loss of cortisol diurnal rhythm (in saliva) with elevated afternoon cortisol levels. The thesis investigated whether any hypercortisolaemia was sustained during the year after delirium, and whether this was associated with deterioration in cognition during the year after hip fracture. Finally, it also tested whether there are high levels of a marker of central nervous system damage (S100B) and of a dementia marker (tau) in CSF in delirium. A prospective observational cohort study was conducted in N=108 patients aged over 60 who had sustained a hip fracture, in whom 40% developed delirium. Participants gave informed consent or if they lacked capacity to give informed consent, this was given by their next of kin. Participants were assessed regularly for delirium, according to DSM IV criteria, during the two weeks after hip fracture. A sample of CSF was collected during the spinal anaesthetic performed for the operation to repair their fracture. Samples of blood and saliva were collected during the two weeks after the hip fracture operation. Participants were visited three, six and twelve months after their hip fracture for further delirium assessment, and a cognitive test battery was completed. Further samples of blood and saliva were collected at these visits. The study found evidence of high levels of cortisol and of S100B in CSF in those with active delirium, but there were no differences in levels of tau or cytokines in CSF. Those with delirium had elevated serum cortisol during the perioperative period, and elevated afternoon salivary cortisol, suggesting flattening of cortisol diurnal rhythm with failure to reach the normal diurnal nadir. After adjusting for confounders in a multivariate logistic regression analysis, serum cortisol was still predictive of delirium, but salivary cortisol AM:PM ratio had a trend towards significance. Those who had persistent delirium features in the months after hip fracture had significantly higher serum cortisol three months after hip fracture. There was a change in serum inflammatory profile in those with delirium, with a shift towards a pro-inflammatory state. Testing the study hypotheses surrounding cognition after delirium was very challenging, due to patient attrition and other factors. Some participants showed a trajectory of cognitive improvement, which was probably due to resolution of delirium during the year after hip fracture. Those with resolved delirium had deficits in verbal and visual memory. This study has improved understanding of the mechanisms of delirium, suggested further avenues for research and identified possible new therapeutic targets.

No study has examined the effect of exercise modality (free weight vs. machine weight) on the acute hormonal response using similar multi-joint exercises. The purpose of this investigation was to examine the effect of resistance exercise modality on acute hormonal responses by comparing the squat and leg press which are multi-joint, and similar in action and lower-body muscle involvement. Ten resistance trained men (21-31 y, 24.7 ± 2.9 y, 179 ± 7 cm, 84.2 ± 10.5 kg) participated in the study. Sessions 1 and 2 determined the participants’ 1-RM in the squat and leg press. During acute heavy resistance exercise testing visits (AHRET), sessions 3 and 4, participants completed 6 sets of 10 repetitions with an initial intensity of 80% of their 1-RM for the squat and leg press exercises. There was a 2 minute rest period between each set. Blood samples were collected before, immediately after, and 15 and 30 minutes after exercise via intravenous catheter during the AHRET visits and were analyzed for testosterone, cortisol, and growth hormone. Lactate, plasma volume change, heart rates and ratings of perceived exertion were also measured. Total work was calculated for external load only and for external load and the body mass used in the exercises. The 4 sessions were counterbalanced and randomized for exercise mode. Testosterone for the squat (Pre: 23.9 ± 8.7 nmol•L-1; IP: 31.4 ± 10.3 nmol•L) and leg press (Pre: 22.1 ± 9.4 nmol•L-1; IP: 26.9 ± 7.8 nmol•L) increased but more significantly after the squat. Growth hormone increased in both the squat (Pre: 0.2 ± 0.2 µg/L; IP: 9.5 ± 7.3 µg/L) and the leg press (Pre: 0.3 ± 0.5 µg/L; IP: 2.8 ± 3.2 µg/L). The increase was significantly higher after the squat compared to the leg press. Cortisol also increased after performing the squat (Pre: 471.9 ± 167.2 nmol•L-1; IP: 603.2 ± 277.6 nmol•L) and leg press (Pre: 463.5 ± 212.4 nmol•L-1; IP: 520.3 ± 270.3 nmol•L), but there was no significant difference between the two modes. The total work was significantly higher in the squat (60509 ± 10759 j) compared to the leg press (42875 ± 7010). The squat exercise is more effective at inducing an acute hormonal response. If the leg press exercise is used, the hormonal response may be reduced, which might lead to reduced training adaptations, especially when only a 90º knee angle ROM is used. To induce the maximal hormonal response to resistance exercise, free weight exercises should be used.

Recreational sport climbing is characterised by self-selected route choices, which place participants under both physiological and psychological stress. This thesis is comprised of four studies, each conducted with experienced climbers, exploring subjective psychological, objective psychophysiological and behavioural responses to anxiety-inducing stressors. Studies One and Two explored the means of protecting a climber in the event of a fall and the relative difficulty of a route. Significant and meaningful differences in self-reported anxiety and climbing performance were found in both studies. However, notably, psychophysiological measures of anticipatory heart rate and cortisol did not result in meaningful differences. Results suggested that situations, atypical of participants’ normal recreation sessions, with an increased likelihood of a climber falling or being unable to complete the route, were likely to be evaluated as threatening, elicit a negative emotional response and disrupt performance. However, the quantitative methods employed in Studies One and Two did not provide an explanation of the processes underlying participant’s anxious response and disrupted performance. Consequently, Study Three qualitatively explored individual experiences of climbers, with a focus on psychological factors that influence performance. The defining characteristics of lead climbing were discussed, as were the potential for taking falls, and/or the anticipation of falling. Further, interviewees described the choices they make, in order to increase or decrease the physical, psychological and technical challenges present. Critically, the choices made by a climber appear to potentiate or limit opportunities to perform optimally. Climber’s decisions were mediated by a number of antecedents, including a climber’s background in the sport, climbing partners and training status. Data suggests that while decisions made by the climbers allow them to engage with the sport on their own terms and exert a level of control over the challenges of their climbing sessions, it is often at the expense of performance. Interestingly, while interviewees were aware of techniques to reduce anxiety and improve performance, few regularly used these in training. Study Four examined the effectiveness of clip drops and repeat practice to reduce anxiety. Results indicated that neither technique resulted in reduced anxiety or improved performance when compared to the control group. While there were small differences in the success rate of participants in the intervention groups, they were less anxious and interpreted their level of self-confidence as more positive, compared to control, it was not possible to differentiate between the two interventions. However, when the combined means were considered there were significant and meaningful differences observed in the post-intervention red-point ascent compared to the initial on-sight. This thesis highlights the difficulty that arises in attempting to quantitatively examine anxiety. While there might not be (a) anxiety in climbers or (b) quantifiable differences between climbers of different abilities, it may be that what is possibly ‘noise’ in data arises due to weaknesses in the markers themselves. The findings of Study Three provide evidence of the true nature of anxiety for climbers, which was not evident from the quantitative markers; as well as the lengths climbers will go to, to avoid anxiety. Climbers’ responses to anxiety were individualised, consequently, generalised interventions may have a limited effect on reducing anxiety to a level which supports performance improvements. It may be that an individualised approach to anxiety reduction and avoidance behaviours has a more significant impact on performance improvement than any of the latest training programmes, equipment or nutritional strategies.

This study examined the effects of rapid and uncompensable core temperature (Tc) acquisition on cerebral oxygenation and haemodynamics, cerebral neural function, decision-making, and rate and magnitude salivary cortisol appearance. Fourteen male subjects (mean age, 33.6 ± 12.1 years) performed an incremental treadmill exercise test to a termination criterion in a control session (CON) and an experimental session (PPE). The incremental treadmill exercise test protocol included an initial 5-minute stage at 3.5 mph and a 0% grade, the second stage was 5-minutes at 3.5 mph at 4% grade, the third stage was 50-minutes at 3.5 mph and an 8% grade, and the final stage was 1-hour at 3.5 mph and a 12% grade. The Instrumentation included a near-infrared spectroscopy (NIRS) monitor, MUSE EEG monitoring system, Equivital integrated physiological monitoring system, Tc capsules, and salivary cortisol oral swabs and ELISA kit for salivary analysis. Important physiological results were significant differences in the physiological strain index (PSI) at all common points of measurement. Important cerebral oxygenation and haemodynamics results were a plateau in left-side prefrontal cortex (PFC) HbO2 and tHb at roughly Tc 38°C in both CON and PPE, 80% of TTT in CON, and 60% of TTT in PPE. Additionally, there was higher left-side PFC activation during PPE as indicated by a significant decrease in TSI % from start to end of exercise and double the decrease in TSI % per minute in PPE when compared to CON. There were no significant differences during the CON session. An analysis of frontal theta EEG power results showed a significant decrease when comparing pre- and post-exercise values during a Go/No-go test in PPE (F(1,13) = 6.069, p ≤ 0.05)). There was also a significant difference when evaluating incorrect responses between pre- and post-exercise values in PPE (F(1,13) = 12.785, p ≤ 0.01)); these differences were not observed during CON. There was also a difference in the rate of cortisol appearance (CON = 0.002 µg dL-1 min-1; PPE = 0.018 µg dL-1 min-1). In the PPE condition, mean cortisol values between start of exercise and the measurement point associated with Tc 38°C and between the start and end of exercise during PPE were significantly different (F(1,13) = 22.71, p ≤ 0.01). Lastly, there was a significant difference between magnitude of cortisol values at the termination between CON and PPE. These data suggest that rapid and uncompensable Tc acquisition during PPE caused an altered cerebral oxygenation and haemodynamic response in the left-side PFC when compared to CON. The left PFC could be working harder to prevent fatigue in PPE. This could have implications for cognitive processes during and/or following exercise in the heat while wearing PPE. These data also suggest rapid and uncompensable Tc acquisition results in decreased cognitive control. This could have implications for individuals whose occupation requires PPE and critical decision making while experiencing rapid Tc heat storage. Lastly, these results show a difference between PPE and CON in regards to rate and magnitude of salivary cortisol appearance, potentially affecting individuals chronically exposed to acute heat stress. Increased acute cortisol concentration decreases anabolic response, cognitive performance, and mood states. The chronic effects of increased cortisol concentration are many: largely related to atherosclerosis development and subsequent cardiovascular disease. Additional issues include anthropometric, endocrine, metabolic, and haemodynamic disturbances. This study makes a strong argument for the rate of thermal acquisition factor. CON and PPE differences in PSI at all measurement points provides justification and support for the changes in other variables. Rapid and uncompensable Tc acquisition needs to be taken into account, as it potentially puts the lives of employees who wear PPE and those around them at risk. / Graduate

Competition for resources plays an important role in natural selection, creating winners and losers. Winners become socially dominant, obtain resources and so increase their fitness at the expense of losers. Provided they are heritable, phenotypic traits promoting competitive success will be inherited by subsequent generations. Thus, while resource dependent traits (e.g. growth) that rely on competitive outcomes are widely recognised as being under strong selection, this is also likely to be the case for those traits that determine competitive ability and social dominance. In addition, competition is expected to be an important source of stress, for example, harassment of subordinates by dominant individuals. Consequently individual fitness may depend not only on the ability to win resources, but also on the ability to cope with stress. This thesis proposes that social dominance is not just a simple consequence of body size or weaponry, but rather that the interplay between growth, repeatable behavioural characteristics (i.e. personality), and the ability to cope with social and environmental stressors are equally important factors. Thus the dynamic of dominance arises, a model that highlights the expectation of complex relationships between traits causal and consequent to social dominance. Here, empirical studies of Xiphophorus sp. are used to test each element in the model. First the concept of individual personality is explored, asking to what extent it is really stable over long periods of time (equivalent to lifespans). Next, the links between behaviour, physiological stress and contest outcome are considered and, using a repeated measures approach, the hypothesis that individuals differ in stress coping style is evaluated. Finally, using a quantitative genetic approach the additive genetic variance-covariance matrix (G) is estimated between behavioural and life history traits under experimentally manipulated levels of competition. In this way the contribution of genetic and environmental effects to the patterns of trait (co)variation that make up the dynamic of dominance is assessed.

The purpose of this study was to monitor cardiovascular and endocrine changes in sedentary and training females during a six week period, and to assess the accuracy of a new, low-invasive sampling methodology (electrosonophoresis). Changes in fitness were measured using oxygen consumption (VO2). The impact on VO2 of sleep quality, sleep duration and alcohol consumption (recorded in sleep logs) was assessed. Cortisol, testosterone and growth hormone levels in plasma were monitored for acute changes following fitness tests, and chronic changes related to training, oral contraceptive use or alcohol consumption. Hormone concentrations in blood and saliva samples were compared to those in interstitial fluid (obtained using electrosonophoresis) to investigate the accuracy of electrosonophoresis. Mean VO2 increased by 3.3 ± 1.3mL/kg/min between Week 1 and Week 5 and the changes detected in heart rate (HR) during the fitness tests suggest that aerobic fitness of the training participants increased across the study. No significant associations between sleep quality, sleep duration or alcohol consumption and VO2 were detected. No acute changes in plasma hormone concentrations following fitness tests were detected. No chronic changes in plasma cortisol or testosterone concentrations were detected, although a non-significant trend towards increased plasma GH levels in training participants was detected. Resting plasma cortisol levels were significantly lower in oral contraceptive users compared with non-users. Plasma testosterone and growth hormone levels were unaffected by oral contraceptive use. Alcohol consumption had no acute detectable effects on plasma concentrations of the three hormones. Plasma testosterone levels were higher in participants who abstained from alcohol, and higher plasma growth hormone levels were detected in heavy drinkers. These results contrast with published reports. Concentrations of the three hormones in interstitial fluid and plasma exhibited highly significant positive correlations (r2 > 0.98) with an interstitial fluid:plasma concentration ratio of about 1:10 in each case. Equations to predict plasma concentrations of cortisol, testosterone and growth hormone from interstitial fluid concentrations have been derived. The electrosonophoretic method apparently provides an accurate, painless, low-invasive method for prediction of the plasma levels of these three hormones. This technology has far-reaching implications for research in human, animal and biomedical fields.

The purpose of the present study was to test the acute effects of a dietary supplement, having as its major ingredient an extract of ginseng, on grip strength, lower body power output, cardiovascular markers, metabolic markers, hormones, and mood state. Twelve experienced resistance-trained men (28.3 ± 5.7 yrs) were randomly administered placebo (P), single dose (SD) and double dose (DD) of the supplement on separate days. Diet and activity levels were kept constant across testing days. On each day, subjects began with the Profile of Mood States (POMSpre1), blood draws (BDpre1), blood pressure (BPpre1), and heart rate (HRpre1) assessments, then ingested the drink and sat quietly for 30 minutes. BDpre2, BPpre2, and HR pre1 were then taken. Subjects performed the grip strength and cycle ergometer tests followed immediately by BDpost, HRpost, and BPpost and POMSpost. The testing session ended with blood draws, heart rates, and blood pressures being taken 30 (post30), 60 (post60), 120 (post120) and 180 (post180) minutes post exercise. Grip strength did not differ between P, SD, or DD treatments. Cycle ergometry peak power (PP), average power (AP) and total work (TW) were significantly higher for the SD and DD than P; however, no significant difference existed between SD and DD treatments. For LH and T significant differences were found among all treatment conditions. There were no significant treatment effects for HR, BP, glucose, insulin, lactate, GH or PRL or for the POMS. There was a significant treatment*time interaction for ACTH (p < .05). Post hoc analysis indicated that at Tpost ACTH was significantly lower for D treatment vs P or S treatments (p < .05) and at Tpost60 ACTH was significantly lower for S and D treatments vs P treatment (p < .05). There was significant differences in C between the D treatment (260.45 ± 15.58 nmol•L-1) and the P (336.08 ± 27.59 nmol•L-1) and S (311.14 ± 21.01 nmol•L-1) treatments (p < .001). There was a significant difference for T:C ratio values among P (0.0810 ± 0.0090), S (0.0960 ± 0.0130) and D (0.1410 ± 0.0190) treatments (p < .001). Acute ingestion of a polynutrient supplement containing a standardized ginseng tract, was able to increase PP, AP, TW LH, and testosterone and decrease ACTH and cortisol. No significant effects were found for GH, PRL, insulin, glucose, lactate, HR, BP or POMS scores. Acute ingestion of a polynutrient supplement was able to increase performance and the anabolic environment in resistance trained men.

Recently, the European Union published regulations regarding the welfare of horses during transport requiring that horses be transported in individual stalls separated by partitions. The objective of this study was to determine if concentrations of cortisol, corticosterone, or dehydroepiandrosterone (DHEA) differed among horses with no prior transport experience when transported in individual stalls versus loose groups. Twenty na�ve yearlings were assigned to either individual stalls or a loose group, then transported for 6 hours. Ten horses were transported per day (5 in stalls and 5 in a loose group) over a two day trial. The experiment was replicated with a second trial 35 days later, and utilized a switchback design where the horses exchanged treatments between trials. Blood samples were collected and analyzed for cortisol, corticosterone, and DHEA concentrations at pre-transport, 2, 4, and 6 h of transport, and at 2 and 4 h after unloading. After Trial 2, the horses? changed housing from group paddocks to stalls and a follow-up experiment was conducted. The data were analyzed using a mixed model repeated measures ANOVA with the animal as the subject, with trial, treatment, sample time, and treatment-sample time interaction in the model with unstructured covariance (SAS 9.1). Differences between sample times within each trial, and pre-transport concentrations between trials, were analyzed using paired t-tests (SPSS 12.0.1). No significant differences were found in hormone concentrations for horses transported in individual stalls versus in loose groups. Horses exhibited a significant elevation in cortisol and corticosterone during transport which returned to pre-transport concentrations by 2 hr after transport (P < 0.01). Mean pre-transport cortisol concentrations rose significantly in Trial 3 (7.87 ng/ml) from Trials 1 (2.71 ng/ml) and 2 (2.84 ng/ml) (P < 0.001). Pre-transport concentrations of DHEA in Trials 1 (482 pg/ml) and 2 (392 pg/ml) also rose significantly in Trial 3 (1607 pg/ml) (P < 0.01). Changes in cortisol and DHEA indicated that transportation was a significant stressor for horses, however, being transported in a loose group versus individual stalls was not different. Also, housing changes from paddocks to stalls resulted in significant increases in pre-transport concentrations of stress-related compounds.