Dietary wild bitter gourd displays selective androgen receptor modulator like activity and improves the muscle decline of orchidectomized mice

2019 ◽  
Vol 10 (1) ◽  
pp. 125-139 ◽  
Author(s):  
Chih-Ling Wang ◽  
Hsiu-Ni Kung ◽  
Ching-Ho Wu ◽  
Ching-jang Huang
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Muscle Function ◽  
Bitter Gourd ◽  
Selective Androgen Receptor Modulator ◽  
Skeletal Muscle Function ◽  
Receptor Modulator ◽  
Selective Androgen Receptor Modulators ◽  
Receptor Modulators

Wild bitter gourd, like selective androgen receptor modulators (SARMs), restored the mass of androgen responsive muscles but not prostate and might improve skeletal muscle function in orchidectomized mice.

scholarly journals Myoanabolic steroids and selective androgen receptor modulators: mechanism of action and perspectives

2009 ◽  
Vol 150 (45) ◽  
pp. 2051-2059 ◽  
Author(s):  
Miklós Tóth
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Conformational Changes ◽  
Anabolic Steroids ◽  
Target Tissue ◽  
Androgenic Activity ◽  
Selective Androgen Receptor Modulators ◽  
Transcriptional Coregulators ◽  
Tissue Selectivity ◽  
Receptor Modulators

Interest in anabolic steroids has been renewed in the last decade with the discovery of tissue-selective androgen receptor modulators exhibiting high myotropic and small androgenic activity. An explanation put forward by us in 1982 for the mechanism of the preferential myotropic effect of nandrolone (19-nortestosterone) exploits the fundamental difference between the 5α-reductase concentrations in skeletal muscle and androgenic target tissue. In androgenic tissue, testosterone is converted to the more potent 5α-dihydrotestosterone whereas nandrolone is converted to a less potent derivative. As 5α-reduction is negligible in skeletal muscle, this explains why nandrolone shows a greater myotropic to androgenic ratio when compared with testosterone. Anabolic steroids that do not undergo 5α-reduction exert myotropic-androgenic dissociation because their effect in androgenic tissues is not amplified by 5α-reduction. Tissue selectivity by receptor modulators may be achieved by inducing specific conformational changes of the androgen receptor that affect its interaction with transcriptional coregulators. Anabolic activity is mediated by the stimulation of ribosomal RNA synthesis therefore regulation of this synthesis by anabolic steroids would deserve detailed studies.

scholarly journals Selective Androgen Receptor Modulator Treatment Improves Muscle Strength and Body Composition and Prevents Bone Loss in Orchidectomized Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4887-4897 ◽  
Author(s):  
Wenqing Gao ◽  
Peter J. Reiser ◽  
Christopher C. Coss ◽  
Mitch A. Phelps ◽  
Jeffrey D. Kearbey ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Androgen Receptor ◽  
Muscle Mass ◽  
Male Rats ◽  
Levator Ani Muscle ◽  
Dependent Manner ◽  
Agonist Activity ◽  
Mineral Density ◽  
Selective Androgen Receptor Modulator ◽  
Receptor Modulator

The partial agonist activity of a selective androgen receptor modulator (SARM) in the prostate was demonstrated in orchidectomized rats. In the current study, we characterized the full agonist activity of S-3-(4-acetylamino-phenoxy)-2-hydroxy-2-methyl-N-(4-nitro-3-trifluoromethyl-phenyl)-propionamide (a structurally related SARM referred to in other publications and hereafter as S-4) in skeletal muscle, bone, and pituitary of castrated male rats. Twelve weeks after castration, animals were treated with S-4 (3 or 10 mg/kg), dihydrotestosterone (DHT) (3 mg/kg), or vehicle for 8 wk. S-4 (3 and 10 mg/kg) restored soleus muscle mass and strength and levator ani muscle mass to that seen in intact animals. Similar changes were also observed in DHT-treated (3 mg/kg) animals. Compared with the anabolic effects observed in muscle, DHT (3 mg/kg) stimulated prostate and seminal vesicle weights moire than 2-fold greater than that observed in intact controls, whereas S-4 (3 mg/kg) returned these androgenic organs to only 16 and 17%, respectively, of the control levels. S-4 (3 and 10 mg/kg) and DHT (3 mg/kg) restored castration-induced loss in lean body mass. Furthermore, S-4 treatment caused a significantly larger increase in total body bone mineral density than DHT. S-4 (3 and 10 mg/kg) also demonstrated agonist activity in the pituitary and significantly decreased plasma LH and FSH levels in castrated animals in a dose-dependent manner. In summary, the strong anabolic effects of S-4 in skeletal muscle, bone, and pituitary were achieved with minimal pharmacologic effect in the prostate. The tissue-selective pharmacologic activity of SARMs provides obvious advantages over steroidal androgen therapy and demonstrates the promising therapeutic utility that this new class of drugs may hold.

scholarly journals Gait disturbances and muscle dysfunction in fibroblast growth factor 2 knockout mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
C. Homer-Bouthiette ◽  
L. Xiao ◽  
Marja M. Hurley
Keyword(s):  
Skeletal Muscle ◽  
Growth Factor ◽  
Muscle Strength ◽  
Fibroblast Growth Factor ◽  
Muscle Function ◽  
Fibroblast Growth Factor 2 ◽  
Fibroblast Growth ◽  
Skeletal Muscle Function ◽  
Age Related ◽  
Gait Disturbances

AbstractFibroblast growth factor 2 (FGF2) is important in musculoskeletal homeostasis, therefore the impact of reduction or Fgf2 knockout on skeletal muscle function and phenotype was determined. Gait analysis as well as muscle strength testing in young and old WT and Fgf2KO demonstrated age-related gait disturbances and reduction in muscle strength that were exacerbated in the KO condition. Fgf2 mRNA and protein were significantly decreased in skeletal muscle of old WT compared with young WT. Muscle fiber cross-sectional area was significantly reduced with increased fibrosis and inflammatory infiltrates in old WT and Fgf2KO vs. young WT. Inflammatory cells were further significantly increased in old Fgf2KO compared with old WT. Lipid-related genes and intramuscular fat was increased in old WT and old Fgf2KO with a further increase in fibro-adipocytes in old Fgf2KO compared with old WT. Impaired FGF signaling including Increased β-Klotho, Fgf21 mRNA, FGF21 protein, phosphorylated FGF receptors 1 and 3, was observed in old WT and old Fgf2KO. MAPK/ ERK1/2 was significantly increased in young and old Fgf2KO. We conclude that Fgf2KO, age-related decreased FGF2 in WT mice, and increased FGF21 in the setting of impaired Fgf2 expression likely contribute to impaired skeletal muscle function and sarcopenia in mice.

scholarly journals Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mohammad Z. Darabseh ◽  
Thomas M. Maden-Wilkinson ◽  
George Welbourne ◽  
Rob C. I. Wüst ◽  
Nessar Ahmed ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Smoking Cessation ◽  
Muscle Fatigue ◽  
Fatigue Resistance ◽  
Systemic Inflammation ◽  
Muscle Function ◽  
Low Grade ◽  
Skeletal Muscle Function ◽  
Tnf Α

AbstractCigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.

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