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Angiotensine et catabolisme

20/04/2017 | Etudes sur les hormones


Skeletal muscle wasting: new role of nonclassical reninangiotensin system
Cabello-Verrugio           Current Opinion in Clinical Nutrition & Metabolic Care: May 2017 - Volume 20 - Issue 3 - p 158–163

Purpose of review: Skeletal muscle can be affected by many physiological and pathological conditions that contribute to the development of muscle weakness, including skeletal muscle loss, inflammatory processes, or fibrosis. Therefore, research into therapeutic treatment alternatives or alleviation of these effects on skeletal muscle is of great importance.

Recent findings: Recent studies have shown that angiotensin (1–7) [Ang-(1–7)] – a vasoactive peptide of the nonclassical axis in the renin–angiotensin system (RAS) – and its Mas receptor are expressed in skeletal muscle. Ang-(1–7), through its Mas receptor, prevents or diminishes deleterious effects induced by skeletal muscle disease or injury. Specifically, the Ang-(1–7)–Mas receptor axis modulates molecular mechanisms involved in muscle mass regulation, such as the ubiquitin proteasome pathway, the insulin-like growth factor type 1/Akt (protein kinase B) pathway, or myonuclear apoptosis, and also inflammation and fibrosis pathways.

Summary: Although further research into this topic and the possible side effects of Ang-(1–7) is necessary, these findings are promising, and suggest that the Ang-(1–7)–Mas axis can be considered a possible therapeutic target for treating patients with muscular disorders.

Effets de l’énanthate de testostérone sur les reins

21/03/2017 | Etudes sur les hormones


Effets de l’énanthate de testostérone sur les reins de rats mâles Wistar soumis à un entraînement en résistance
S. Karbasia         Science & Sports Available online 17 March 2017

Les Stéroïdes Anabolisants Androgéniques (AAS) sont les produits dopants les plus utilisés dans le sport et sont susceptibles d’exercer des effets secondaires sur le rein. Le but de cette étude était de déterminer les effets d’une injection d’énanthate de testostérone (TE) lors d’un entrainement en résistance (RT) de 8 semaines chez des rats Wistar mâles.

Matériels et méthodes

Vingt-huit rats Wistar mâles ont été randomisés en en 4 groupes : C : contrôle, RT : exercice en résistance + placebo, TE : énanthate de testostérone, et l’association des deux (TE + RT). Le Protocole d’entrainement en résistance consiste en la montée d’une échelle (5 fois à 3 reprises) pendant huit semaines. Le TE et le placebo (20 mg/kg de poids corporel, en IM) ont été injectés deux fois par jour. A la fin, les rats ont été euthanasiés pour réaliser l’analyse biochimique du sérum et l’examen histopathologique du tissu rénal.


Dans le groupe RT, une augmentation significative (p

< 0,05) de la créatinine sérique a été observée en comparaison avec les groupes TE et TE + RT. Une hyperémie modérée et une congestion du tissu ont été observées dans tous les groupes de traitement.


Nous ne mettons pas en évidence de détérioration de la filtration glomérulaire après 8 semaines de TE (20 mg/kg) mais d’autres études sont nécessaires pour préciser l’effet rénal de ce traitement.

Rôle de la sirtuine 1 dans l’hypertrophie

02/03/2017 | Etudes sur les hormones et Etudes Musculation et Etudes Anti-âge


SIRT1 may play a crucial role in overload induced hypertrophy of skeletal muscle
Erika Koltai J physiol 2017

Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well-studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus, and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in SIRT1 content and activity (P

< 0.001). SIRT1-regulated Akt, eNOS, GLUT4 levels were also induced in hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased FOXO1 and increased K48 polyubiquitination also suggest that SIRT1 could also be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1, and Nampt levels. Our results reveal a strong agreement between SIRT1 levels and activity, SIRT1 regulated pathways, and overload-induced hypertrophy.

These findings, along with the well-known regulatory

roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing.

Le mystère des aliments riche en mélatonine

31/12/2016 | Etudes sur les hormones et Etudes Compléments alimentaires et Etudes Anti-âge


Are the proposed benefits of melatonin-rich foods too hard to swallow?
David J. Kennaway     Critical Reviews in Food Science and Nutrition   2016 Pages 958-962

Melatonin has been proposed as a potent anti-oxidant, and its presence in many plants and foods has been suggested to be beneficial for health. Indeed, the concentrations of melatonin in blood and the melatonin metabolite 6 sulphatoxymelatonin in urine have been found to increase significantly after ingestion of melatonin-rich foods. In this review, the studies have been critically evaluated in light of the reported plant melatonin concentrations and our knowledge of pharmacokinetics of orally administered pure melatonin. In the case of studies involving measurement of plasma melatonin following ingestion of beer or fruits, the reported increase in melatonin is not consistent with the amount of melatonin ingested. Similarly, the amount of melatonin metabolite excreted following ingestion of melatonin-rich foods greatly exceeded the amount of melatonin ingested.

It is concluded that studies reporting the appearance of melatonin in blood and its metabolites in urine following ingestion of melatonin-rich foods are flawed. While there may be health benefits for certain foods, it is difficult to accept that these are due to their low melatonin content.


Une blessure peut avoir des conséquences psychologiques graves

08/12/2016 | Echauffement et blessures


Are severe musculoskeletal injuries associated with symptoms of common mental disorders among male European professional footballers?
Knee Surgery, Sports Traumatology, Arthroscopy December 2016, Volume 24, Issue 12, pp 3934–3942   Vincent Gouttebarge


To explore the associations of severe musculoskeletal injuries (joint and muscles) and surgeries with symptoms of common mental disorders (distress, anxiety/depression, sleeping disturbance, adverse alcohol behaviour , smoking, adverse nutrition behaviour) among male European professional footballers.


Cross-sectional analyses were conducted on electronic questionnaires completed by professional footballers recruited from the national players’ unions of Finland, France, Norway, Spain or Sweden. The number of severe (time loss of more than 28 days) musculoskeletal injuries (total, joint, muscle) and surgeries during a professional football career was examined through four questions, while symptoms of common mental disorders were evaluated through validated scales.


A total of 540 professional footballers (mean age of 27 years; 54 % playing in the highest leagues) participated in the study. Sixty-eight per cent of the participants had already incurred one or more severe joint injuries and 60 % one or more severe muscle injuries. Prevalence of symptoms of common mental disorders ranged from 3 % for smoking to 37 % for anxiety/depression and 58 % for adverse nutrition behaviour. The number of severe musculoskeletal injuries during a football career was positively correlated with distress, anxiety and sleeping disturbance, while the number of surgeries was correlated with adverse alcohol behaviour and smoking. Professional footballers who had sustained one or more severe musculoskeletal injuries during their career were two to nearly four times more likely to report symptoms of common mental disorders than professional footballers who had not suffered from severe musculoskeletal injuries.


It can be concluded that the number of severe musculoskeletal injuries and surgeries during a career is positively correlated and associated with symptoms of common mental disorders among male European professional footballers. This study emphasises the importance of applying a multidisciplinary approach to the clinical care and support of professional footballers, especially when a player faces lengthy periods without training and competition as a consequence of recurrent severe joint or muscle injuries.

Le Viagra est-il aussi un anti-aromatase?

01/12/2016 | Etudes Perte de poids et Etudes Anti-âge et Etudes sur les boosters sexuels et la sexualité


Effect of sildenafil on human aromatase activity: From in vitro structural analysis to catalysis and inhibition in cells
The Journal of Steroid Biochemistry and Molecular Biology Volume 165, Part B, January 2017, Pages 438–447       Roberta Baravalle

• Human aromatase binds the drug sildenafil showing a Type II spectrum.
• EPR spectroscopy shows that sildenafil does not directly bind heme iron.
• Sildenafil acts as a mixed and partial inhibitor on human aromatase.
• Aromatase inhibition by sildenafil is confirmed in ST14A and MCF-7 cells.

Aromatase catalyses the conversion of androgens into estrogens and is a well-known target for breast cancer therapy. As it has been suggested that its activity is affected by inhibitors of phosphodiesterase-5, this work investigates the potential interaction of sildenafil with aromatase. This is carried out both at molecular level through structural and kinetics assays applied to the purified enzyme, and at cellular level using neuronal and breast cancer cell lines.

Sildenafil is found to bind to aromatase with a KD of 0.58 ± 0.05 μM acting as a partial and mixed inhibitor with a maximal inhibition of 35 ± 2%. Hyperfine sublevel correlation spectroscopy and docking studies show that sildenafil binds to the heme iron via its 6th axial water ligand.

These results also provide information on the starting molecular scaffold for the development of new generations of drugs designed to inhibit aromatase as well as phosphodiesterase-5, a new emerging target for breast cancer therapy.

Le curcuma est-il un inhibiteur de la 5 alpha réductase?

27/11/2016 | Etudes Compléments alimentaires et Etudes Anti-âge et Etudes sur les boosters sexuels et la sexualité


A new label-free screen for steroid 5α-reductase inhibitors using LC-MS
Steroids Volume 116, December 2016, Pages 67–75       Jukkarin Srivilai

• A novel assay for 5 alpha reductase (S5αR) activity determination based on LC-MS quantitation of DHT.
• The assay showed high reproducibility and selectivity with Z′ factor of 0.77.
• The method was successfully used to quantify S5αR inhibitory activity of some herbal extracts.

Steroid 5α-reductase (S5αR) plays an important role in metabolizing testosterone into active androgen dihydrotestosterone (DHT) which is involved in many androgen dependent disorders, such as androgenic alopecia, benign prostatic hyperplasia and acne. The method for screening for S5αR inhibition is key in finding new antagonists. In this study, the label-free S5αR inhibitory assay using LC-MS was developed. S5αR type 1 enzyme was obtained from LNCaP prostate cancer cells. The enzymatic assay was optimised for enzyme-substrate (testosterone) concentration, NADPH-cofactor concentration, solvent tolerance, enzyme activity stability and incubation time. The developed assay was validated by measuring the signal to background ratio (S/B), the signal to noise ratio (S/N), the signal window (SW) and the zeta factor Z′ in accordance with published bioassay guidelines. The enzymatic reaction was performed in 96-well plates and DHT formation was determined by LC-MS. S/B, S/N, SW and Z′ factor were well above acceptable criteria and the reproducibility was good using Z′ factor other 3 days and further validated by dutasteride and finasteride inhibition. The method was successfully applied to quantify S5αR inhibitory activity of some Thai herbal extracts.

Two plant extracts, Impatiens balsamina L. and Curcuma longa L. showed IC50 at 5.4 ± 0.2 and 9.0 ± 1.2 μg mL−1 and are therefore promising sources of new S5αR inhibitors. The assay has high selectability and reproducibility and suited to medium throughput screening required by phytochemistry.

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