SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Anabolic steroid

40

Performance-enhancing substances (PESs) are used commonly by children and adolescents in attempts to improve athletic performance. More recent data reveal that these same substances often are used for appearance-related reasons as well. PESs include both legal over-the-counter dietary supplements and illicit pharmacologic agents. This report reviews the current epidemiology of PES use in the pediatric population, as well as information on those PESs in most common use. Concerns regarding use of legal PESs include high rates of product contamination, correlation with future use of anabolic androgenic steroids, and adverse effects on the focus and experience of youth sports participation. The physical maturation and endogenous hormone production that occur in adolescence are associated with large improvements in strength and athletic performance. For most young athletes, PES use does not produce significant gains over those seen with the onset of puberty and adherence to an appropriate nutrition and training program.

Concepts: Metabolism, Hormone, Testosterone, Androgen, Adolescence, Steroid, Puberty, Anabolic steroid

39

Cancer cachexia negatively impacts cancer-related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment.

Concepts: Epidemiology, Cancer, Oncology, Cancer staging, Cachexia, Weight loss, Muscle atrophy, Anabolic steroid

34

Previous strength training with or without the use of anabolic steroids facilitates subsequent re-acquisition of muscle mass even after long intervening periods of inactivity. Based on in vivo and ex vivo microscopy we here propose a cellular memory mechanism residing in the muscle cells. Female mice were treated with testosterone propionate for 14 days, inducing a 66% increase in the number of myonuclei and a 77% increase in fibre cross sectional area. Three weeks after removing the drug, fibre size was decreased to the same level as in sham treated animals, but the number of nuclei remained elevated for at least 3 months (>10% of the mouse lifespan). At this time, when the myonuclei-rich muscles were exposed to overload-exercise for 6 days, the fibre cross sectional area increased by 31% while control muscles did not grow significantly. We suggest that the lasting, elevated number of myonuclei constitutes a cellular memory facilitating subsequent muscle overload hypertrophy. Our findings might have consequences for the exclusion time of doping offenders. Since the ability to generate new myonuclei is impaired in the elderly our data also invites speculation that it might be beneficial to perform strength training when young in order to benefit in senescence.

Concepts: Metabolism, Muscle, Testosterone, Muscle contraction, Muscular system, Nerve, Anabolic steroid, Bodybuilding

34

Alcohol (ethanol) and resistance exercise can independently affect circulating bioavailable testosterone concentration. PURPOSE: The purpose of this study was to examine the testosterone bioavailability and the anabolic endocrine milieu in response to acute ethanol ingestion following a bout of heavy resistance exercise. METHODS: Eight resistance trained men (mean ± SD: 25.3 ± 3.2 yrs, 87.7 ± 15.1 kg, 177 ± 7 cm) completed two identical acute heavy resistance exercise tests (AHRET: six sets of 10 repetitions of Smith machine squats) separated by 1 week. Post-AHRET participants consumed either 1.086 g of grain ethanol per kg lean mass (EtOH condition) or no ethanol (Placebo condition). Blood samples were collected immediately before exercise (PRE), immediately after exercise (IP), and every 20 min postexercise for 300 min. Samples following IP were pooled into phases (20-40 min, 60-120 min, and 140-300 min after exercise) and analyzed for total (TT) and free testosterone (FT), sex hormone binding globulin (SHBG), cortisol, and estradiol. RESULTS: Peak blood ethanol concentration (0.088 ± 0.015 g·dl) was achieved 60-90 min post-exercise. TT and FT was elevated significantly (p≤0.05) at IP for both conditions. At 140-300 min post-exercise TT, FT, and free androgen index were significantly higher for EtOH (TT: 22.5 ± 12.5 nmol·l ; FT: 40.5 ± 7.6 pmol·l) than for Placebo (TT: 13.9 ± 6.8 nmol·l; FT: 22.7 ± 10.0 pmol·l). No differences between conditions were noted for SHBG, Cortisol, or Estradiol. CONCLUSION: Post-exercise ethanol ingestion affects the hormonal milieu including testosterone concentration and bioavailability during recovery from resistance exercise.

Concepts: Hormone, Ethanol, Luteinizing hormone, Testosterone, Sex hormone-binding globulin, Estradiol, Adrenal cortex, Anabolic steroid

32

Bodybuilding competitions are becoming increasingly popular. Competitors are judged on their aesthetic appearance and usually exhibit a high level of muscularity and symmetry and low levels of body fat. Commonly used techniques to improve physique during the preparation phase before competitions include dehydration, periods of prolonged fasting, severe caloric restriction, excessive cardiovascular exercise and inappropriate use of diuretics and anabolic steroids. In contrast, this case study documents a structured nutrition and conditioning intervention followed by a 21 year-old amateur bodybuilding competitor to improve body composition, resting and exercise fat oxidation, and muscular strength that does not involve use of any of the above mentioned methods. Over a 14-week period, the Athlete was provided with a scientifically designed nutrition and conditioning plan that encouraged him to (i) consume a variety of foods; (ii) not neglect any macronutrient groups; (iii) exercise regularly but not excessively and; (iv) incorporate rest days into his conditioning regime. This strategy resulted in a body mass loss of 11.7 kg’s, corresponding to a 6.7 kg reduction in fat mass and a 5.0 kg reduction in fat-free mass. Resting metabolic rate decreased from 1993 kcal/d to 1814 kcal/d, whereas resting fat oxidation increased from 0.04 g/min to 0.06 g/min. His capacity to oxidize fat during exercise increased more than two-fold from 0.24 g/min to 0.59 g/min, while there was a near 3-fold increase in the corresponding exercise intensity that elicited the maximal rate of fat oxidation; 21% V̇O2max to 60% V̇O2max. Hamstring concentric peak torque decreased (1.7 to 1.5 Nm/kg), whereas hamstring eccentric (2.0 Nm/kg to 2.9 Nm/kg), quadriceps concentric (3.4 Nm/kg to 3.7 Nm/kg) and quadriceps eccentric (4.9 Nm/kg to 5.7 Nm/kg) peak torque all increased. Psychological mood-state (BRUMS scale) was not negatively influenced by the intervention and all values relating to the Athlete’s mood-state remained below average over the course of study. This intervention shows that a structured and scientifically supported nutrition strategy can be implemented to improve parameters relevant to bodybuilding competition and importantly the health of competitors, therefore questioning the conventional practices of bodybuilding preparation.

Concepts: Metabolism, Nutrition, Competition, Obesity, Muscle, Strength training, Exercise physiology, Anabolic steroid

31

It is well established that regimented resistance training can promote increases in muscle hypertrophy. The prevailing body of research indicates that mechanical stress is the primary impetus for this adaptive response and studies show that mechanical stress alone can initiate anabolic signalling. Given the dominant role of mechanical stress in muscle growth, the question arises as to whether other factors may enhance the post-exercise hypertrophic response. Several researchers have proposed that exercise-induced metabolic stress may in fact confer such an anabolic effect and some have even suggested that metabolite accumulation may be more important than high force development in optimizing muscle growth. Metabolic stress pursuant to traditional resistance training manifests as a result of exercise that relies on anaerobic glycolysis for adenosine triphosphate production. This, in turn, causes the subsequent accumulation of metabolites, particularly lactate and H(+). Acute muscle hypoxia associated with such training methods may further heighten metabolic buildup. Therefore, the purpose of this paper will be to review the emerging body of research suggesting a role for exercise-induced metabolic stress in maximizing muscle development and present insights as to the potential mechanisms by which these hypertrophic adaptations may occur. These mechanisms include increased fibre recruitment, elevated systemic hormonal production, alterations in local myokines, heightened production of reactive oxygen species and cell swelling. Recommendations are provided for potential areas of future research on the subject.

Concepts: Oxygen, Metabolism, Adenosine triphosphate, Oxidative phosphorylation, Force, Anabolic steroid, Anabolism, Muscle hypertrophy

29

BACKGROUND: The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. METHODS: Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analysed using HPLC and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. RESULTS: Over the concentration range of 2 to 8% the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HLPC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 M despite a ten-fold excess of testosterone. CONCLUSION: This study reports that in an in vitro supersome-based assay, the key steroid-metabolising enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the health implications.

Concepts: Protein, Alcohol, Metabolism, Ethanol, Testosterone, Caffeic acid, Anabolic steroid, Chlorogenic acid

28

Herbal and dietary supplements (HDS) are used increasingly both in the United States and worldwide and HDS induced liver injury in the U.S. has increased proportionally. Current challenges in the diagnosis and management of HDS-induced liver injury were the focus of a 2-day research symposium sponsored by the American Association for the Study of Liver Disease and the National Institutes of Health. HDS-induced liver injury now accounts for 20% of cases of hepatotoxicity in the United States based on research data. The major implicated agents include anabolic steroids, green tea extract, and multi-ingredient nutritional supplements (MINS). Anabolic steroids marketed as bodybuilding supplements typically induce a prolonged cholestatic, but ultimately self-limiting liver injury that has a distinctive serum biochemical as well as histological phenotype. Green tea extract and many other products, in contrast, tend to cause an acute-hepatitis like injury. Currently, however, the majority of cases of HDS-associated liver injury are due to MINS, and the component responsible for the toxicity is usually unknown or can only be suspected. HDS-induced liver injury presents many clinical and research challenges, in diagnosis, identification of the responsible constituents, treatment and prevention. Also important are improvements in regulatory oversight of non-prescription products to guarantee their constituents and insure purity and safety. The confident identification of injurious ingredients within HDS will require strategic alignments among clinicians, chemists, and toxicologists. The ultimate goal should be to prohibit or more closely regulate potentially injurious ingredients and thus promote public safety. This article is protected by copyright. All rights reserved.

Concepts: United States, Testosterone, Camellia sinensis, Green tea, All rights reserved, Anabolic steroid, Copyright, Hepatotoxicity

28

Current approaches to diagnosing testosterone deficiency do not consider the physiological consequences of various testosterone levels or whether deficiencies of testosterone, estradiol, or both account for clinical manifestations.

Concepts: Function, Estrogen, Testosterone, Estradiol, Steroid, Anabolic steroid

28

Introduction: The development and potential clinical use of tissue-selective androgen receptor modulators (SARMs) have advanced tremendously over the past few years. A key aspect of SARMs is the ability to clearly differentiate between the anabolic and androgenic activities. SARMs provide therapeutic opportunities in a variety of diseases, including muscle wasting associated with burns, cancer, end-stage renal disease, osteoporosis, frailty and hypogonadism. Areas covered: The aim of the present paper is to summarize the current standing of research and development of SARMs and plausible molecular mechanisms underlying the potential for selective modulation of androgen receptor (AR) by different ligands. This paper also provides an update on SARM discovery paradigms for preclinical evaluations. Expert opinion: Promising results have been obtained in preclinical investigations and initial clinical trials, but long-term safety, tolerability and efficacy studies in patients are still necessary. Preclinically, improving knowledge of tissue selectivity at the molecular level, developing AR selectivity transcription profile, exploring in vitro/in vivo correlation, along with expanding selectivity evaluation among more androgen responsive tissues would accelerate the discovery of a new generation of more selective and safer clinical candidates, minimize false leads and hasten development of effective approaches for an expanded range of clinical conditions.

Concepts: Kidney, Gene expression, Effectiveness, Cellular differentiation, Testosterone, Androgen, Anabolic steroid, Selective androgen receptor modulator