Purinergic signaling influences the neuroinflammatory outcomes of a testosterone-derived synthetic in female rats: Resistance training protective effects on brain health.

Physical exercise is recognized as a non-pharmacological approach to treat and protect against several neuroinflammatory conditions and thus to prevent brain disorders. However, the interest in ergogenic resources by athletes and bodybuilding practitioners is widespread and on the rise. These substances shorten the process of performance gain and improve aesthetics, having led to the prominent use and abuse of hormones in the past years. Recent evidence has shown that the purinergic system, composed of adenine nucleotides, nucleosides, enzymes, and receptors, participates in a wide range of processes within the brain, such as neuroinflammation, neuromodulation, and cellular communication. Here, we investigated the effects of the anabolic androgenic steroid (AAS) testosterone (TES) at a dose of 70 mg/kg/week in female rats and the neuroprotective effect of resistance exercise related to the purinergic system and oxidative stress parameters. Our findings showed a decrease in ATP and ADO hydrolysis in treated and trained animals. Furthermore, there was an increase in the density of purinoceptors (P2X7 and A2A) and inflammatory markers (IBA-1, NRLP3, CASP-1, IL-1ß, and IL-6) in the cerebral cortex of animals that received AAS. On the other hand, exercise reversed neuroinflammatory parameters such as IBA-1, NLRP3, CASP-1, and IL-1ß and improved antioxidant response and anti-inflammatory IL-10 cytokine levels. Overall, this study shows that the use of TES without indication or prescription disrupts brain homeostasis, as demonstrated by the increase in neuroinflammation, and that the practice of exercise can protect brain health.

Association between neuronal degeneration and supraphysiological doses of two types of anabolic steroids in rat brain.

The anabolic androgenic steroids (AAS) are natural compounds that are precursors or derivatives of testosterone and, as a consequence of indiscriminate use, cause irreversible neuronal effects. For this study, 70 brain samples were used from male Wistar rats, separated into 14 groups, divided into: control, sedentary, and exercise groups; in the concentrations: 5 mg, 10 mg, and 15 mg. Two different AAS were used: Testosterone Cypionate (TC) and Nandrolone Decanoate (ND). The encephali followed all the conventional histological procedures, for further analysis of the estimates of neuron bodies of the Locus coeruleus; also being carried out the techniques of the Tunnel Assay and Von Kossa staining. The results obtained show significant values different from the control group: Testosterone Cypionate (TCS): 5 mg (25,00 ± 4,47); 10 mg (23,67 ± 4,45) and 15 mg (21,93 ± 5,65), as well as for Nandrolone Decanoate (ND) in the doses: 5 mg (23,40 ± 3,81); 10 mg (22,80 ± 3,80) and 15 mg (22,80 ± 4,54) being the values of the control group (CGS) 34,27 ± 6,06. For the groups that exercised, the values were: TCT 5 mg 20,87 ± 3,23; TCT 10 mg 21,93 ± 4,91 and TCT 15 mg 21,47 ± 4,36 while, the Nandrolone Decanoate (ND) groups, in the different doses were: NDT 5 mg 21,53 ± 4,34; NDT 10 mg 23,53 ± 1,68 and NDT 15 mg 23,40 ± 2,20, also expressing significant values different from the control group. When comparing the sedentary control group with the animals that exercised, a statistically significant difference was observed being: CGS 34,27 ± 6,06; TCT 5 mg; 20,87 ± 3,23; NDT 5 mg 21,53 ± 4,34; TCT 10 mg 21,93 ± 4,91; NDT 10 mg 23,53 ± 1,68; TCT 15 mg 21,47 ± 4,36 and NDT 15 mg 23,40 ± 2,20. The results of this study, point out that both steroids drastically reduce neuronal density in the Locus coeruleus area inferring that, the possible cause of neuronal death is necrosis, caused by intracellular calcium imbalance.

Effects of Low-to-Moderate Doses of Anabolic Steroids on Lipid Profile and Muscle Hypertrophy in Resistance Training Practitioners: A Systematic Review with Meta-Analysis

Abstract Background: The use of androgenic anabolic steroids (AAS) is prevalent among young bodybuilders, motivated by aesthetic results. Although the medical community condemns this practice for its potential deleterious effect, we must recognize the need for more scientific research on the likelihood and magnitude of the adverse events. Objective: To evaluate whether high-quality, scientific evidence supports that AAS negatively affect lipid profile and promote muscle hypertrophy in resistance training practitioners. Methods: A systematic review of the literature of randomized clinical trials was conducted in the PubMed / Medline, Scielo and Science direct databases. The searches were conducted by two independent researchers by June 2018. A significance level of 5% was considered in the analysis. Results: Six clinical trials involving 170 resistance training practitioners were included. A significant heterogeneity was found in studies evaluating the effects of AAS on lipid profile and muscle hypertrophy (I² = 97, 95 and 91%, respectively), with no significant effects on HDL-cholesterol (-5.62mg/dL, 95%CI −12.10, 0.86, p= 0.09), LDL-cholesterol (7.76 mg/dL, 95%CI −9.70, 25.23, p= 0.57) and muscle hypertrophy (2.44kg 95%CI 0.02, 4.86, p=0.05). Conclusion: Current evidence does not support that low-to-moderate doses of AAS cause serious negative effects on lipid profile or promote muscle hypertrophy in resistance training practitioners.

The effects of anabolic-androgenic steroids on DNA damage in bodybuilders' blood lymphocytes.

BACKGROUND: Nowadays bodybuilders use anabolic steroids frequently. Abuse of these substances can cause significant side effects; therefore, we aim to investigate the effect of anabolic steroids on DNA damage in bodybuilders' blood lymphocytes. METHODS AND MATERIALS: This case-control study was performed on 36 male bodybuilders in Gonabad. The case group included bodybuilders with a history of taking anabolic-androgenic steroids (n = 18), and the control group composed of bodybuilders who did not use anabolic-androgenic steroids (n = 18). Intravenous blood samples were obtained and then the lymphocytes, cells and electrophoresis of blood were extracted. Afterward, the coloured slides and DNA damage were measured using a fluorescent microscope and CometScore software. The DNA damage was compared using t-tests . RESULTS: Results showed that there was no significant difference between age, marital status, BMI, systolic and diastolic blood pressure in the case and control group. However, parameters related to the DNA damage including tail length, percent tail DNA, and tail moment were significantly higher in the case group. CONCLUSION: The use of anabolic-androgenic steroids increases DNA damage in the bodybuilders' blood lymphocytes.

Left ventricular dyssynchrony and post-systolic shortening in young bodybuilders using anabolic-androgenic steroids.

Left ventricular (LV) remodeling, characterized by increased LV hypertrophy and depressed systolic and diastolic function, is observed in strength-trained athletes who use anabolic-androgenic steroids (AAS). Previous studies suggested a pathological remodeling with an increase in cardiac fibrosis in these athletes, which could promote intraventricular dyssynchrony. In this context, this study evaluated LV dyssynchrony in strength-trained athletes using AAS, hypothesizing that the use of AAS would lead to an increase in post-systolic shortening. Forty-four male subjects (aged 20-40 yr) were divided into three age-matched groups: strength-trained athletes using (users, n = 14) or not (nonusers, n = 15) AAS and healthy sedentary men (controls, n = 15). After completing a survey, each participant was assessed with two-dimensional (2D)-strain echocardiography. LV dyssynchrony was quantified using the standard deviation (SD) of the time to peak for longitudinal strain of the 18 LV-segments (from the apical 4, 3, and 2 chambers views), the longitudinal strain delay index (LSDI), and the segmental post-systolic index (PSI). Users showed mean AAS dosages of 564 ± 288 mg[Formula: see text]wk-1 with a mean protocol duration of 12 ± 6 wk and a history of use of 4.7 ± 1.8 yr. They exhibited a greater LV mass index and depressed systolic and diastolic function when compared with both nonusers and controls. The decrease in LV strain in users was predominantly observed at the interventricular septum level (-16.9% ± 2.5% vs. -19.2% ± 1.8% and -19.0% ± 1.6% in users, nonusers, and controls, respectively, P < 0.01). Users showed higher SD than controls (43 ± 8 ms vs. 32 ± 5 ms, respectively, P < 0.01). The LSDI was significantly higher in users compared with both nonusers and controls (-23.4 ± 9.5 vs. -15.9 ± 9.3 and -9.8 ± 3.9, respectively, P < 0.01). PSI, calculated on the basal inferoseptal, basal anteroseptal, and basal inferolateral segments, were also greater in users compared with the two other groups. Our results reported an increase in LV dyssynchrony in young AAS users that brought new evidences of a pathologic cardiac remodeling in this specific population.NEW & NOTEWORTHY Illicit androgenic anabolic steroids (AAS) use is widespread, but data on LV dyssynchrony are lacking, although it could be increased by a higher prevalence of myocardial fibrosis reported in this population. In AAS users, the decrease in LV strain was predominantly observed in interventricular segments. All dyssynchrony indices were higher in AAS users and several segments exhibited post-systolic shortening. These results showed an association between AAS consumption, LV remodeling, and dyssynchrony.

Testosterone Reduces Body Fat in Male Mice by Stimulation of Physical Activity Via Extrahypothalamic ERα Signaling.

Testosterone (T) reduces male fat mass, but the underlying mechanisms remain elusive, limiting its clinical relevance in hypogonadism-associated obesity. Here, we subjected chemically castrated high-fat diet-induced adult obese male mice to supplementation with T or the nonaromatizable androgen dihydrotestosterone (DHT) for 20 weeks. Both hormones increased lean mass, thereby indirectly increasing oxygen consumption and energy expenditure. In addition, T but not DHT decreased fat mass and increased ambulatory activity, indicating a role for aromatization into estrogens. Investigation of the pattern of aromatase expression in various murine tissues revealed the absence of Cyp19a1 expression in adipose tissue while high levels were observed in brain and gonads. In obese hypogonadal male mice with extrahypothalamic neuronal estrogen receptor alpha deletion (N-ERαKO), T still increased lean mass but was unable to decrease fat mass. The stimulatory effect of T on ambulatory activity was also abolished in N-ERαKO males. In conclusion, our work demonstrates that the fat-burning action of T is dependent on aromatization into estrogens and is at least partially mediated by the stimulation of physical activity via extrahypothalamic ERα signaling. In contrast, the increase in lean mass upon T supplementation is mediated through the androgen receptor and indirectly leads to an increase in energy expenditure, which might also contribute to the fat-burning effects of T.

Valproate selectively suppresses adolescent anabolic/androgenic steroid-induced aggressive behavior: implications for a role of hypothalamic γ-aminobutyric acid neural signaling.

Pubertal male Syrian hamsters (Mesocricetus auratus) treated with anabolic/androgenic steroids (AASs) during adolescence (P27-P56) display a highly intense aggressive phenotype that shares many behavioral similarities with pathological aggression in youth. Anticonvulsant drugs like valproate that enhance the activity of the γ-aminobutyric acid (GABA) neural system in the brain have recently gained acceptance as a primary treatment for pathological aggression. This study examined whether valproate would selectively suppress adolescent AAS-induced aggressive behavior and whether GABA neural signaling through GABAA subtype receptors in the latero-anterior hypothalamus (LAH; an area of convergence for developmental and neuroplastic changes that underlie aggression in hamsters) modulate the aggression-suppressing effect of this anticonvulsant medication. Valproate (1.0-10.0 mg/kg, intraperitoneal) selectively suppressed the aggressive phenotype in a dose-dependent fashion, with the effective anti-aggressive effects beginning at 5 mg/kg, intraperitoneally. Microinfusion of the GABAA receptor antagonist bicuculline (7.0-700 ng) into the LAH reversed valproate's suppression of AAS-induced aggression in a dose-dependent fashion. At the 70 ng dose of bicuculline, animals expressed the highly aggressive baseline phenotype normally observed in AAS-treated animals. These studies provide preclinical evidence that the anticonvulsant valproate selectively suppresses adolescent, AAS-induced aggression and that this suppression is modulated, in part, by GABA neural signaling within the LAH.

Common questions and misconceptions about creatine supplementation: what does the scientific evidence really show?

Supplementing with creatine is very popular amongst athletes and exercising individuals for improving muscle mass, performance and recovery. Accumulating evidence also suggests that creatine supplementation produces a variety of beneficial effects in older and patient populations. Furthermore, evidence-based research shows that creatine supplementation is relatively well tolerated, especially at recommended dosages (i.e. 3-5 g/day or 0.1 g/kg of body mass/day). Although there are over 500 peer-refereed publications involving creatine supplementation, it is somewhat surprising that questions regarding the efficacy and safety of creatine still remain. These include, but are not limited to: 1. Does creatine lead to water retention? 2. Is creatine an anabolic steroid? 3. Does creatine cause kidney damage/renal dysfunction? 4. Does creatine cause hair loss / baldness? 5. Does creatine lead to dehydration and muscle cramping? 6. Is creatine harmful for children and adolescents? 7. Does creatine increase fat mass? 8. Is a creatine 'loading-phase' required? 9. Is creatine beneficial for older adults? 10. Is creatine only useful for resistance / power type activities? 11. Is creatine only effective for males? 12. Are other forms of creatine similar or superior to monohydrate and is creatine stable in solutions/beverages? To answer these questions, an internationally renowned team of research experts was formed to perform an evidence-based scientific evaluation of the literature regarding creatine supplementation.

Immunohistomorphometric and Hormonal Analysis of the Pituitary Gonadotropic Cells After Application of the Nandrolone Decanoate and Swimming Training in Adult Male Rats.

The aim of the study was to investigate the effects of chronic nandrolone decanoate treatment and/or swimming training on immunohistomorphometric parameters on rat pituitary gonadotropic cells. Male Wistar albino rats, 10 weeks old, were classified into four groups: control (T−N−), nandrolone (T−N+), swimming training (T+N−), and swimming training with nandrolone (T+N+). The T+ groups swam for 4 weeks, 1 h/day, 5 days/week. The N+ groups received nandrolone decanoate (20 mg/kg) once per week for 4 weeks. Pituitary tissue sections were processed and stained for immunohistochemical analysis and immunofluorescence. The volume density of luteinizing hormone (LH) cells was decreased by 48% in T−N+ and for 35% in the T+N+ group. The volume density of follicle-stimulating hormone (FSH) cells was decreased by 39% in T−N+ and for 30% in T+N+ compared to the control. Nandrolone alone, or combined with swimming training, decreased the number of LH/FSH cells compared to the control. The levels of the immunofluorescent signal of LH/FSH cells were increased in all experimental groups. Nandrolone alone decreased the serum level of LH by 17%, whereas swimming training alone increased FSH levels by 11% compared to the control. Serum levels of testosterone were increased in all experimental groups. Nandrolone alone, or combined with swimming training, decreased immunohistomorphometric parameters of gonadotropic cells, whereas the levels of immunofluorescent signal were increased.

Anabolic androgenic steroids exert a selective remodeling of the plasma lipidome that mirrors the decrease of the de novo lipogenesis in the liver.

INTRODUCTION: The abuse of anabolic androgenic steroids (AASs) is a source of public concern because of their adverse effects. Supratherapeutic doses of AASs are known to be hepatotoxic and regulate the lipoproteins in plasma by modifying the metabolism of lipids in the liver, which is associated with metabolic diseases. However, the effect of AASs on the profile of lipids in plasma is unknown. OBJECTIVES: To describe the changes in the plasma lipidome exerted by AASs and to discuss these changes in the light of previous research about AASs and de novo lipogenesis in the liver. METHODS: We treated male Wistar rats with supratherapeutic doses of nandrolone decanoate and testosterone undecanoate. Subsequently, we isolated the blood plasma and performed lipidomics analysis by liquid chromatography-high resolution mass spectrometry. RESULTS: Lipid profiling revealed a decrease of sphingolipids and glycerolipids with palmitic, palmitoleic, stearic, and oleic acids. In addition, lipid profiling revealed an increase in free fatty acids and glycerophospholipids with odd-numbered chain fatty acids and/or arachidonic acid. CONCLUSION: The lipid profile presented herein reports the imprint of AASs on the plasma lipidome, which mirrors the downregulation of de novo lipogenesis in the liver. In a broader perspective, this profile will help to understand the influence of androgens on the lipid metabolism in future studies of diseases with dysregulated lipogenesis (e.g. type 2 diabetes, fatty liver disease, and hepatocellular carcinoma).

Enzymatic Synthesis of Anabolic Steroid Glycosides by Glucosyltransferase from Terribacillus sp. PAMC 23288.

The application of steroids has steadily increased thanks to their therapeutic effects. However, alternatives are required due their severe side effects; thus, studies on the activities of steroid derivatives are underway. Sugar derivatives of nandrolone, which is used to treat breast cancer, as well as cortisone and prednisone, which reduce inflammation, pain, and edema, are unknown. We linked O-glucose to nandrolone and testosterone using UDP-glucosyltransferase (UGT-1) and, then, tested their bioactivities in vitro. Analysis by NMR showed that the derivatives were 17ß-nandrolone ß-D-glucose and 17ß-testosterone ß-D-glucose, respectively. The viability was higher and cytotoxicity was evident in PC12 cells incubated with rotenone and, testosterone derivatives, compared to the controls. SH-SY5Y cells incubated with H2O2 and nandrolone derivatives remained viable and cytotoxicity was attenuated. Both derivatives enhanced neuronal protective effects and increased the amounts of cellular ATP.

Serotonin type-3 receptors differentially modulate anxiety and aggression during withdrawal from adolescent anabolic steroid exposure.

Male Syrian hamsters (Mesocricetus auratus) administered anabolic/androgenic steroids during adolescent development display increased aggression and decreased anxious behavior during the adolescent exposure period. Upon withdrawal from anabolic/androgenic steroids, this neurobehavioral relationship shifts and hamsters exhibit decreased aggression and increased anxious behavior. This study investigated the hypothesis that alterations in anterior hypothalamic signaling through serotonin type-3 receptors modulate the behavioral shift between adolescent anabolic/androgenic steroid-induced aggressive and anxious behaviors during the withdrawal period. To test this, hamsters were administered anabolic/androgenic steroids during adolescence then withdrawn from drug exposure for 21 days and tested for aggressive and anxious behaviors following direct pharmacological manipulation of serotonin type-3 receptor signaling within the latero-anterior hypothalamus. Blockade of latero-anterior hypothalamic serotonin type-3 receptors both increased aggression and decreased anxious behavior in steroid-treated hamsters, effectively reversing the pattern of behavioral responding normally observed during anabolic/androgenic steroid withdrawal. These findings suggest that the state of serotonin neural signaling within the latero-anterior hypothalamus plays an important role in behavioral shifting between aggressive and anxious behaviors following adolescent exposure to anabolic/androgenic steroids.

Combined effects of exercise training and high doses of anabolic steroids on cardiac autonomic modulation and ventricular repolarization properties in rats.

Several studies have reported that high doses of synthetic anabolic androgenic steroids (AAS) can have serious negative effects on health, including the cardiovascular system. The aim of this study was to evaluate the combined effects of AAS and exercise training on ventricular repolarization and cardiac autonomic modulation in rats. Male Wistar rats were allocated into 4 groups: sedentary rats treated with vehicle, sedentary rats treated with nandrolone decanoate, swimming-trained rats treated with vehicle, and swimming-trained rats treated with nandrolone decanoate. Ventricular repolarization was evaluated by electrocardiographic analysis of QT interval and QT dispersion. Cardiac autonomic modulation was assessed by heart rate variability. Our results show that AAS increased QT interval and QT dispersion in sedentary rats treated with nandrolone decanoate as compared to sedentary rats treated with vehicle, indicating AAS-induced ventricular repolarization abnormalities. When rats treated with nandrolone decanoate were subjected to concomitant exercise training, ventricular repolarization was normalized. On the other hand, AAS-induced reduction in cardiac parasympathetic modulation was not prevented by exercise training. In conclusion, AAS produced cardiac autonomic dysfunction and ventricular repolarization disturbances in rats. Combining an exercise training protocol during the AAS treatment attenuated the ventricular repolarization abnormalities and did not prevent cardiac autonomic dysfunction.

The complex and bidirectional interaction between sex hormones and exercise performance in team sports with emphasis on soccer.

A constant topic reported in the lay press is the effect of sex hormones on athletic performance and their abuse by athletes in their effort to enhance their performance or to either boost or sidestep their hard, protracted, and demanding training regimens. However, an issue that it is almost never mentioned is that the athletic training itself affects the endogenous production of androgens and estrogens, while also being affected by them. Among sports, soccer is a particularly demanding activity, soccer players needing to possess high levels of endurance, strength, and both aerobic and anaerobic capacity, with the very great physiological, metabolic, physical, and psychological exertion required of the players being both influenced by sex steroids and, reciprocally, affecting sex steroid levels. This review focuses on the currently available knowledge regarding the complex relationship between athletic training and competition and sex steroid hormone adaptation to the demands of the exercise effort. In the first part of the review, we will examine the effects of endogenous testosterone, estrogen, and adrenal androgens on athletic performance both during training and in competition. In the second part, we will explore the reciprocal effects of exercise on the endogenous sex hormones while briefly discussing the recent data on anabolic androgenic steroid abuse.

Combined nestorone-testosterone gel suppresses serum gonadotropins to concentrations associated with effective hormonal contraception in men.

BACKGROUND: Novel male-based contraceptives are needed to broaden family planning choices. A progestin, Nestorone® (Nes) gel, plus a testosterone (T) gel suppresses sperm concentrations to levels associated with effective contraception in normal men. However, administration of two gels on different parts of the body daily is impractical. OBJECTIVE: Compare the effectiveness of daily application of a single, combined 8.3 mg Nes-62.5 mg T gel (Nes-T) vs. 62.7 mg T gel to suppress serum FSH and LH concentrations to ≤1.0 IU/L (a threshold associated with suppression of sperm concentrations to ≤1 million and effective contraception) and to compare the pharmacokinetics of serum Nes and T concentrations between the gel groups. DESIGN: We conducted a 28-day, double-blind, controlled trial of 44 healthy men randomized to daily Nes-T or T gel with measurement of hormones at baseline, treatment, and recovery and during 24-h pharmacokinetic studies on days 1 and 28 of treatment. RESULTS: Of the subjects who met pre-defined inclusion criteria, 84% of the Nes-T group suppressed serum gonadotropin concentrations to ≤1.0 IU/L at days 21-28 vs. 16.7% in the T group (p < 0.001). On day 1, Nes concentrations rose significantly above baseline by 2 h and continued to rise up to 24 h after Nes-T gel application. Nes concentrations were not detectable in the T group. Serum total T concentrations rose and were significantly higher in the T gel group compared to the Nes-T group at 24 h on day 1 and days 11, 14, and 21 (p < 0.01). There were no serious adverse events in either group. About 80% of the subjects reported satisfaction with both gels. CONCLUSION: Daily Nes-T gel effectively and safely suppresses serum gonadotropins and is acceptable to most men. It should be studied further in efficacy trials of hormonal male contraception.

Cognitive performance and structural brain correlates in long-term anabolic-androgenic steroid exposed and nonexposed weightlifters.

OBJECTIVE: To test for associations between long-term anabolic-androgenic steroid (AAS) use and cognitive functioning, and establish a candidate neuronal basis by assessing the associations between cognitive performance and brain morphology both in users and nonusers. METHOD: Eighty four previous or current AAS-users and 69 non-AAS-using male weightlifters aged 19-75 years (mean 32.6, SD 8.8) underwent MRI of the brain and a comprehensive neuropsychological test battery. Performance on fine motor speed, speed of processing, learning and memory, working memory, executive functioning, and problem solving was compared between the groups, and between AAS users with short versus long AAS exposure. Associations between cognitive scores and regional cortical thickness and arealization defined using FreeSurfer were tested using linear models. RESULTS: Relative to nonexposed, AAS-exposed weightlifters performed significantly worse on several cognitive domains, independent of age, education, verbal IQ, and exposure to classical drugs of abuse. Strongest effects were observed for speed of processing (ηp2 = .07), working memory (ηp2 = .08) and problem solving (ηp2 = .09). Longer duration of AAS-use was associated with poorer memory function (ηp2 = .11). Within AAS users, individuals with better memory and working memory performance had with thicker frontoparietal cortex and larger medial frontal surface area, respectively. CONCLUSIONS: Prolonged high-dose AAS use is associated with poorer cognitive function across multiple domains, and the observed regional associations between cortical brain morphometry and memory and working memory performance may suggest differential brain-based mechanisms. The public, health care professionals, and policymakers should be aware that use of AAS in large doses potentially could lead to poorer brain health and cognition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Modulation of exercise training related adaptation of body composition and regulatory pathways by anabolic steroids.

Anabolic steroids have a long history of abuse in amateur and professional athletics. However, their interaction with training and the resulting effects on body composition and tissue adaptation, relying on a concert of factors and pathways, remain under investigation. This study aims at investigating the changes of body composition and the expression of selected genes and pathways essential for this adaptation process. Therefore, male wistar rats were treated with the anabolic steroid metandienone in two groups (n = 16; metandienone, metandienone + exercise) alongside with control groups (n = 16; control, exercise). Following a 6-week steep-angle treadmill training protocol, weight of organs, visceral fat and muscles was determined. M. gastrocnemius was histologically assessed by ATPase staining, mRNA and protein levels of factors of regeneration, hypertrophy and myogenesis and selected master regulators and markers were determined. Results show additive effects of anabolic steroids and exercise on body, tibia and reproductive organs weight. Mm. gastrocnemius and soleus weight was increased by training but not anabolic steroids. Muscle fiber diameter and composition remained unchanged. Visceral fat mass and fat cell size was affected by training and anabolic steroids but no additive effects could be observed. Exercise and anabolic steroids result in a complex regulation of the expression of genes in M. Gastrocnemius involved in skeletal muscle metabolism, hypertrophy, inflammation and regeneration. In summary, our data suggests distinct molecular mechanisms involved in the adaptation of the skeletal muscle to anabolic androgenic steroids and exercise. Metandienone treatment neither results in skeletal muscle hypertrophy nor liver-toxic effects but in an induction of skeletal muscle regeneration and an activation of endocrine negative feedback. Moreover our study demonstrates that visceral fat and bone responds with higher sensitivity to ASS and exercise than the skeletal muscle. This apparent plasticity of adipose and bone tissue rather than skeletal muscle could indicate a potentially superior future role of fat rather than muscle related parameters to detect and AAS abuse in a biologic passport strategy in professional athletes.

Anabolic-androgen steroids effects on bioenergetics responsiveness of synaptic and extrasynaptic mitochondria.

We hypothesized that supraphysiological administration of the anabolic-androgenic steroids (AAS) like testosterone (TEST) and nandrolone decanoate (NAND) might differentially affect synaptic and extrasynaptic components of mitochondrial bioenergetics, thereby resulting in memory impairment. Oil (VEH), NAND or TEST (15 mg/Kg) were daily administered to male CF-1 albino mice for 19-days. We evaluated in the synaptosomes and extrasynaptic mitochondria, Ca2+ influx/efflux, membrane potential ΔÑ°m, oxidative respiratory states, dehydrogenases activity, H2O2 production, Tau phosphorylation, and spatial memory in the Morris water maze (MWM). In synaptosomes, both AAS increased Ca2+ influx and Na+ dependent efflux. In extrasynaptic mitochondria, NAND increased the Ca2+ influx. NAND prominently impaired ΔÑ°m formation and dissipation in synaptosomal and extrasynaptic mitochondria, while the effect of TEST was less pronounced. TEST increased the Reserve Respiratory Capacity in synaptosomes, and NAND decreased dehydrogenases activity in synaptic and extrasynaptic mitochondria. Also, NAND increased H2O2 production by synaptosomes and extrasynaptic mitochondria. NAND increased pTauSer396 in synaptosomes. Both AAS did not impair memory performance on MWM. We highlight that high doses of NAND cause neurotoxic effects to components of synaptic and extrasynaptic mitochondrial bioenergetics, like calcium influx, membrane potential and H2O2 production. TEST was less neurotoxic to synaptic and extrasynaptic mitochondrial bioenergetics responses.

The CASTRO study: Unsafe sexual behaviors and illicit drug use among gay and bisexual men who use anabolic steroids.

BACKGROUND AND OBJECTIVES: The majority of anabolic androgenic steroid (AAS) studies have focused on the general male population. Approximately 15% of gay or bisexual men are seropositive for HIV and many AASs are administered via injection. Thus, AAS use among gay and bisexual men likely poses a greater risk of spreading infectious disease. Gay and bisexual men who use AAS were compared with non-users regarding self-reported seropositivity for HIV and hepatitis B and C, sexual behaviors and injection practices, illicit drug and alcohol use, and psychiatric disorders. METHODS: The CASTRO (Castro Anabolic Steroid Research Observation) study was a 108-item cross-sectional survey of 153 gay and bisexual men who exercise. Data collection occurred outside four gyms in the San Francisco Castro District. RESULTS: The lifetime prevalence of AAS use among gay and bisexual men in the study was 21.6%. AAS users and non-users did not differ in self-reported seropositivity for HIV or hepatitis B and C, but AAS users reported higher rates of male-male condomless anal sex in the past year (84.8 vs 60.8%, p < .01) than non-users. More AAS users used ecstasy and methamphetamines (39.4 vs 16.7%, p < .01 and 18.2 vs 5.0%, p = .01, respectively) than non-users. DISCUSSION AND CONCLUSIONS: Gay and bisexual men who used AAS were more likely to engage in unsafe sexual behaviors and use illicit drugs relative to non-users. Multiple factors place AAS users at higher risks for spreading infectious diseases. SCIENTIFIC SIGNIFICANT: Our study suggests increased infectious disease risk among gay and bisexual men who use AAS. (Am J Addict 2019;XX:1-10).