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AR Up-Regulation by Androgen Treatment

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  • heavyiron
    replied
    Originally posted by Kaladryn View Post
    Duchaine was talking about AR multiplication from AAS in the mid 90s on misc.fitness.weights.
    Yup, the theory was out there at the time but no one could conclusively prove it until the late 90's. Duchane was ahead of his time.

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  • Kaladryn
    replied
    Duchaine was talking about AR multiplication from AAS in the mid 90s on misc.fitness.weights.

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  • Baris
    replied
    I remember reading this study and was amazed by the increase in so few days, adding to that that the dosage was 15 mg a day. I was like: Imagine 500 mg of test a week which is like so many more times potent than anavar oxandrolone.

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  • heavyiron
    replied
    This study demonstrated for the first time in humans an increase in skeletal muscle ARs after anabolic intervention. Moreover, these data suggest that OX induced an increase in AR expression as a mechanism for the increase in net muscle protein synthesis in just 5 days of administration!



    J Clin Endocrinol Metab. 1999 Aug;84(8):2705-11.

    Short-term oxandrolone administration stimulates net muscle protein synthesis in young men.

    Sheffield-Moore M, Urban RJ, Wolf SE, Jiang J, Catlin DH, Herndon DN, Wolfe RR, Ferrando AA.
    Department of Surgery, University of Texas Medical Branch, and Shriners Burn Hospital for Children, Galveston 77550, USA. [email protected]

    Abstract

    Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone [Oxandrin (OX)], a synthetic analog of testosterone, would improve net muscle protein synthesis and transport of amino acids across the leg. Six healthy men [22+/-1 (+/-SE) yr] were studied in the postabsorptive state before and after 5 days of oral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femoral arterio-venous sampling and muscle biopsy. The precursor-product method was used to determine muscle protein fractional synthetic rates. Fractional breakdown rates were also directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I and androgen receptor (AR) were determined using RT-PCR. Model-derived muscle protein synthesis increased from 53.5+/-3 to 68.3+/-5 (mean+/-SE) nmol/min.100 mL/leg (P < 0.05), whereas protein breakdown was unchanged. Inward transport of amino acids remained unchanged with OX, whereas outward transport decreased (P < 0.05). The fractional synthetic rate increased 44% (P < 0.05) after OX administration, with no change in fractional breakdown rate. Therefore, the net balance between synthesis and breakdown became more positive with both methodologies (P < 0.05) and was not different from zero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like growth factor I mRNA concentrations. We conclude that short term OX administration stimulated an increase in skeletal muscle protein synthesis and improved intracellular reutilization of amino acids. The mechanism for this stimulation may be related to an OX-induced increase in AR expression in skeletal muscle.


    PMID: 10443664 [PubMed - indexed for MEDLINE]

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  • Dr Pangloss
    replied
    Nice. This suggests that androgens work by upregulating satellite cell differentiation; it also explains the androgen receptor upregulation noted in the past (about 1.5-2 fold) as due to high levels of androgen receptor expression in newly differentiated satellite cells.

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  • heavyiron
    started a topic AR Up-Regulation by Androgen Treatment

    AR Up-Regulation by Androgen Treatment

    In this study 600mg per week of Testosterone Enanthate increased the number of Androgen Receptors in healthy men after 20 weeks of administration.


    Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment

    Indrani Sinha-Hikim, Wayne E. Taylor, Nestor F. Gonzalez-Cadavid, Wei Zheng and Shalender Bhasin
    Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059

    Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059. E-mail: [email protected].


    Abstract

    Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression. AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis. Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nM testosterone and 30 nM dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression. These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.

    Full study;

    http://jcem.endojournals.org/cgi/con...ull/89/10/5245
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