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Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens.

Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens. Research Abstract Details 

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  • Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens. Abstract Text:

    mei hua hongMei Hua Hong,hong sunHong Sun,cheng he jinCheng He Jin,mark chapmanMark Chapman,junlian huJunlian Hu,william changWilliam Chang,kelven burnettKelven Burnett,jon rosenJon Rosen,andres negro-vilarAndres Negro-Vilar,jeffrey n minerJeffrey N Miner,

    Although it is evident that androgens increase muscle mass and strength, little is known about the critical molecular targets of androgens in skeletal muscle. In rodents, the skeletal alpha-actin gene is a tissue-specific gene expressed only in the levator ani and other skeletal muscles but not in the prostate or preputial gland, the well-known androgen target tissue. We identified tissue-specific androgen-regulated genes in the skeletal muscle in rats after oral administration of androgens and focused on androgen-dependent up-regulation of the skeletal alpha-actin gene. To investigate the mechanism of action, an in vitro system with various cell lines and a series of deletion mutants of the alpha-actin promoter were used. The human skeletal alpha-actin promoter was activated by androgens in the muscle cell line C2C12 but not in the liver, prostate, or breast cancer cell lines in which exogenous human androgen receptor is expressed. The sequence of the promoter is sufficient for cell-specific androgen response, providing a model for the tissue specificity demonstrated in vivo. Using a series of deletion mutants, the androgen response can be maintained using just the proximal promoter region. The importance of androgen regulation of this small portion of the human skeletal alpha-actin promoter was demonstrated by the correlation between muscle and the alpha-actin promoter activity for an array of selective androgen receptor modulators (SARMs), including an orally active SARM LGD2226. Taken together, the results suggest that the regulation of skeletal alpha-actin by androgens/SARMs may represent an important model system for understanding androgen anabolic action in the muscle.

    Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens. Publishing Authors By Initials

    mh hongMH Hong,h sunH Sun,ch jinCH Jin,m chapmanM Chapman,j huJ Hu,w changW Chang,k burnettK Burnett,j rosenJ Rosen,a negro-vilarA Negro-Vilar,jn minerJN Miner,

    For similar abstracts research abstracts see: abstracts research

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    Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens. Journal Published:

    PUBLICATION TYPE: Journal Article

    Journal: Endocrinology

    VOLUME: 149

    Page Numbers: 1103-12

    Journal Abbreviation: Endocrinology

    ISSN: 0013-7227

    DAY: 6

    MONTH: 12

    YEAR: 2007

    Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens. Information

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    LANGUAGE: eng

    NlmUniqueID: 375040

    Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens. Keywords Mesh Terms:

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    Grant and Affiliation Information for Cell-Specific Activation of the Human Skeletal {alpha}-Actin by Androgens.

    AFFILIATION: Department of Molecular and Cell Biology, Ligand Pharmaceuticals Inc., 10275 Science Center Drive, San Diego, California 92121. mhong@ligand.com.

    Country: United States

    United States Research PublicationUnited States Research Publication

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    MEDLINETA: Endocrinology

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