Circulating adrenal and gonadal steroid hormones heterogeneity in active young males and the contribution of 11-oxy androgens.

The classical androgens, testosterone and dihydrotestosterone, together with dehydroepiandrosterone, the precusrsor to all androgens, are generally included in diagnostic steroid evaluations of androgen excess and deficiency disorders and monitored in androgen replacement and androgen suppressive therapies. The C11-oxy androgens also contribute to androgen excess disorders and are still often excluded from clinical and research-based steroids analysis. The contribution of the C11-oxy androgens to the androgen pool has not been considered in androgen deficiency. An exploratory investigation into circulating adrenal and gonadal steroid hormones in men was undertaken as neither the classical androgens nor the C11-oxy androgens have been evaluated in the context of concurrent measurement of all adrenal steroid hormones. Serum androgens, mineralocorticoids, glucocorticoids, progesterones and androgens were assessed in 70 healthy young men using ultra high performance supercritical fluid chromatography and tandem mass spectrometry. Testosterone, 24.5 nmol/L was the most prominent androgen detected in all participants while dihydrotestosterone, 1.23 nmol/L, was only detected in 25% of the participants. The 11-oxy androgens were present in most of the participants with 11-hydroxyandrostenedione, 3.37 nmol, in 98.5%, 11-ketoandrostenedione 0.764 in 77%, 11-hydroxytestosterone, 0.567 in 96% and 11-ketotestosterone: 0.440 in 63%. A third of the participants with normal testosterone and comparable 11-ketotestosterone, had significantly lower dehydroepiandrosterone (p < 0.001). In these males 11-hydroxyandrostenedione (p < 0.001), 11-ketoandrostenedione (p < 0.01) and 11-hydroxytestosterone (p < 0.006) were decreased. Glucocorticoids were also lower: cortisol (p < 0.001), corticosterone (p < 0.001), cortisone (p < 0.006) 11-dehydrocorticosterone (p < 0.001) as well as cortisol:cortisone (p < 0.001). The presence of dehydroepiandrosterone was associated with 16-hydroxyprogesterone (p < 0.001), which was also significantly lower. Adrenal and gonadal steroid analysis showed unexpected steroid heterogeneity in normal young men. Testosterone constitutes 78% of the circulating free androgens with the 11-oxy androgens abundantly present in all participants significantly contributing 22%. In addition, a subset of men were identified with low circulating dehydroepiandrosterone who showed altered adrenal steroids with decreased glucocorticoids and decreased C11-oxy androgens. Analysis of the classical and 11-oxy androgens with the additional measurement of dehydroepiandrosterone and 16-hydroxyprogesterone may allow better diagnostic accuracy in androgen excess or deficiency.

The influence of environmental and core temperature on cyclooxygenase and PGE2 in healthy humans.

Whether cyclooxygenase (COX)/prostaglandin E2 (PGE2) thermoregulatory pathways, observed in rodents, present in humans? Participants (n = 9) were exposed to three environments; cold (20 °C), thermoneutral (30 °C) and hot (40 °C) for 120 min. Core (Tc)/skin temperature and thermal perception were recorded every 15 min, with COX/PGE2 concentrations determined at baseline, 60 and 120 min. Linear mixed models identified differences between and within subjects/conditions. Random coefficient models determined relationships between Tc and COX/PGE2. Tc [mean (range)] increased in hot [+ 0.8 (0.4-1.2) °C; p < 0.0001; effect size (ES): 2.9], decreased in cold [- 0.5 (- 0.8 to - 0.2) °C; p < 0.0001; ES 2.6] and was unchanged in thermoneutral [+ 0.1 (- 0.2 to 0.4) °C; p = 0.3502]. A relationship between COX2/PGE2 in cold (p = 0.0012) and cold/thermoneutral [collapsed, condition and time (p = 0.0243)] was seen, with higher PGE2 associated with higher Tc. A within condition relationship between Tc/PGE2 was observed in thermoneutral (p = 0.0202) and cold/thermoneutral [collapsed, condition and time (p = 0.0079)] but not cold (p = 0.0631). The data suggests a thermogenic response of the COX/PGE2 pathway insufficient to defend Tc in cold. Further human in vivo research which manipulates COX/PGE2 bioavailability and participant acclimation/acclimatization are warranted to elucidate the influence of COX/PGE2 on Tc.

Skeletal Muscle Signaling Following Whole-Body and Localized Heat Exposure in Humans.

This study identified the changes in hypertrophy/atrophy and mitochondrial-related signaling in human skeletal muscle following whole-body (WB) and localized single leg (SL) heat treatment. Nine active male participants were administered either 60 min of passive WB (44-50°C, 50% humidity) or SL (water-perfused suit at 49.5 ± 1.4°C) heat treatment at least 1 week apart in a counterbalanced order. The untreated leg during SL was considered as control (CON). Core, skin, and quadriceps muscle temperature were monitored throughout the experimental trials. Muscle microbiopsy samples were obtained prior to (PRE), and 30 min and 3 h post (POST) following heat treatment. Muscle temperature increased with time (p < 0.0001) in both WB and SL, with no differences between conditions (38.8 ± 0.5°C vs. 38.1 ± 0.6°C, p = 0.065). Core temperature increased only following WB, and was significantly higher compared with SL (39.1 ± 0.3°C vs. 37.1 ± 0.1, p < 0.0001). Compared with PRE, WB up-regulated the phosphorylation status of the majority of the Akt/mTOR pathway (Akt, mTOR, S6K1, rpS6, and p-eIF4E; p ≤ 0.050), with the exception of 4EBP1 (p = 0.139). WB also increased the mRNA of HSPs 72, 90, and 25 (all p < 0.021), and increased or tended to increase the phosphorylation of FOXO1 (p = 0.066) and FOXO3a (p = 0.038). In addition, most (NRF1, NRF2, COX2, and COX4-I2; all p ≤ 0.050), but not all (CS, Cyt c, and COX4-I1; p > 0.441) mRNA content indicative of mitochondrial biogenesis were increased following WB, with no changes evident in these parameters in SL or CON (all p > 0.090). These results indicate that 1 h of WB heat treatment enhanced anabolic (Akt/mTOR), mitochondrial, and cyto-protective signaling (HSP), with a concomitant possible inhibition of FOXO transcription factors.

The Effects of Inhaled Terbutaline on 3-km Running Time-Trial Performance.

Terbutaline is a prohibited drug except for athletes with a therapeutic use exemption certificate; terbutaline's effects on endurance performance are relatively unknown. Purpose: To investigate the effects of 2 therapeutic (2 and 4 mg) inhaled doses of terbutaline on 3-km running time-trial performance. Methods: A total of 8 men (age 24.3 [2.4] y; weight 77.6 [8] kg; and height 179.5 [4.3] cm) and 8 women (age 22.4 [3] y; weight 58.6 [6] kg; and height 163 [9.2] cm) free from respiratory disease and illness provided written informed consent. Participants completed 3-km running time trials on a nonmotorized treadmill on 3 separate occasions following placebo and 2- and 4-mg inhaled terbutaline in a single-blind, repeated-measures design. Urine samples (15 min postexercise) were analyzed for terbutaline concentration. Data were analyzed using 1-way repeated-measures analysis of variance, and significance was set at P < .05 for all analyses. Results: No differences were observed for completion times (1103 [201] s, 1106 [195] s, 1098 [165] s; P = .913) for the placebo or 2- and 4-mg inhaled trials, respectively. Lactate values were higher (P = .02) after 4 mg terbutaline (10.7 [2.3] mmol·L-1) vs placebo (8.9 [1.8] mmol·L-1). Values of forced expiratory volume in the first second of expiration (FEV1) were greater after inhalation of 2 mg (5.08 [0.2]; P = .01) and 4 mg terbutaline (5.07 [0.2]; P = .02) compared with placebo (4.83 [0.5] L) postinhalation. Urinary terbutaline concentrations were mean 306 (288) ng·mL-1 and 435 (410) ng·mL-1 (P = .2) and peak 956 ng·mL-1 and 1244 ng·mL-1 after 2 and 4 mg inhaled terbutaline, respectively. No differences were observed between the male and female participants. Conclusions: Therapeutic dosing of terbutaline does not lead to an improvement in 3-km running performance despite significantly increased FEV1. The findings suggest that athletes using inhaled terbutaline at high therapeutic doses to treat asthma will not gain an ergogenic advantage during 3-km running performance.

The Effect of 400 µg Inhaled Salbutamol on 3 km Time Trial Performance in a Low Humidity Environment.

The Objectives of the study were to investigate whether 400 µg inhaled salbutamol influences 3 km running time-trial performance and lung function in eucapnic voluntary hyperpnoea positive (EVH+ve) and negative (EVH-ve) individuals. Fourteen male participants (22.4 ± 1.6yrs; 76.4 ± 8.7kg; 1.80 ± 0.07 m); (7 EVH+ve; 7 EVH-ve) were recruited following written informed consent. All participants undertook an EVH challenge to identify either EVH+ve (↓FEV1>10%) or EVH-ve (↓FEV1<10%). Participants performed three separate 3 km running time-trials in a low-humidity (20-25%) environment on a non-motorized treadmill, 15 minutes following inhalation of salbutamol (400 µg), placebo (non-active inhalant) or control (no inhalant), in a randomized, single-blind, repeated measures design. Forced vital capacity maneuvers were performed at baseline, 10 minutes post inhalation and post time-trial. Time to complete 3 km and lung function data were analyzed using mixed model repeated measures ANOVA. Significance was assumed at p < 0.05. All EVH+ve participants had FEV1 falls from baseline between 10-25% post-challenge. There was no difference in performance time between trial conditions in EVH+ve (1012.7 ± 129.6s; 1002.4 ± 123.1s; 1015.9 ± 113.0s) (p = 0.774) and EVH-ve (962.1 ± 99.2s; 962.0 ± 76.2s; 950.8 ± 84.9s) (p = 0.401) groups for salbutamol, placebo and control trials, respectively. Exercising heart rate was significantly higher (p = 0.05) in the salbutamol trial (183 ± 8 beatsˑmin-1) compared to control (180 ± 9 beatsˑmin-1) with a trend towards significance (p=0.06) in the placebo trial (179 ± 9 beatsˑmin-1) for the pooled groups, no differences were seen between trials in groups individually. There was an increase in FEV1 in both EVH+ve (4.01 ± 0.8L; 4.26 ± 0.7L; 4.25 ± 0.5L) and EVH-ve (4.81 ± 0.4L; 5.1 ± 0.4L; 5.1 ± 0.5L) groups which was significant post-inhalation (p = 0.01; p = 0.02), but not post-time-trial (p = 0.27; p = 0.06), respectively, following salbutamol. EVH+ve participants did not demonstrate significant falls (>10% from baseline) in FEV1 following any time-trial. Administration of 400µg inhaled salbutamol does not improve 3 km time-trial performance in either mild EVH+ve or EVH-ve individuals despite significantly increased HR and FEV1.

The ergogenic effect of long-term use of high dose salbutamol.

OBJECTIVE: Investigate the effect of inhaling 1600 µg salbutamol for 6 weeks on endurance, strength, and power performances. DESIGN: Randomized double-blind, mixed-model repeated measures. PARTICIPANTS: Sixteen male athletes (mean ± SD: age, 20.1 ± 1.6 years; height, 179.9 ± 8.2 cm; weight, 74.6 ± 9.1 kg). INTERVENTIONS: Participants were assigned to either a placebo inhaler (PLA) or inhaled 1600 µg salbutamol group (SAL). Over 6 weeks, participants inhaled PLA or SAL and completed 4 training sessions per week that focused on endurance, strength, and power. MAIN OUTCOME MEASURES: Participants completed the assessments of peak oxygen consumption (V[Combining Dot Above]O2peak), 3-km time trial, vertical jump height, 1 repetition maximum (1RM) bench and leg press, and peak torque knee flexion and extension. Assessments were undertaken at baseline, week 3, and week 6. RESULTS: Over the 6 weeks, PLA and SAL groups improved V[Combining Dot Above]O2peak (51.7 ± 4.7 vs 56.8 ± 7.1 mL·min·kg; 53.1 ± 6.1 vs 55.0 ± 6.7 mL·min·kg); 3-km running time trial (988.6 ± 194.6 vs 947.5 ± 155.5 seconds; 1040.4 ± 187.4 vs 1004.2 ± 199.4 seconds); 1RM bench press (65.7 ± 15.4 vs 70.3 ± 13.8 kg; 64.3 ± 14.0 vs 72.5 ± 15.3 kg); and leg press (250.0 ± 76.4 vs 282.5 ± 63.6 kg; 217.9 ± 54.0 vs 282.8 ± 51.9 kg). The SAL group did not improve significantly greater in any endurance or strength and power measure when compared with the PLA group. CONCLUSIONS: Inhaling 1600 µg salbutamol daily over 6 weeks does not result in significant improvements in endurance, or strength and power performances. CLINICAL RELEVANCE: Athletes using inhaled salbutamol to treat bronchoconstriction during exercise on a daily basis will not gain an advantage over nonasthmatic athletes not using inhaled salbutamol.