Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10582
Title: Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice.
Authors: MacLean, Helen E;Chiu, W S Maria;Notini, Amanda J;Axell, Anna-Maree;Davey, Rachel A;McManus, Julie F;Ma, Cathy;Plant, David R;Lynch, Gordon S;Zajac, Jeffrey D
Affiliation: Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia. hmaclean@unimelb.edu.au
Issue Date: 7-Apr-2008
Citation: Faseb Journal : Official Publication of the Federation of American Societies For Experimental Biology 2008; 22(8): 2676-89
Abstract: To identify mechanisms of anabolic androgen action in muscle, we generated male and female genomic androgen receptor (AR) knockout (ARKO) mice, and characterized muscle mass, contractile function, and gene expression. Muscle mass is decreased in ARKO males, but normal in ARKO females. The levator ani muscle, which fails to develop in normal females, is also absent in ARKO males. Force production is decreased from fast-twitch ARKO male muscle, and slow-twitch muscle has increased fatigue resistance. Microarray analysis shows up-regulation of genes encoding slow-twitch muscle contractile proteins. Real-time PCR confirms that expression of genes encoding polyamine biosynthetic enzymes, ornithine decarboxylase (Odc1), and S-adenosylmethionine decarboxylase (Amd1), is reduced in ARKO muscle, suggesting androgens act through regulation of polyamine biosynthesis. Altered expression of regulators of myoblast progression from proliferation to terminal differentiation suggests androgens also promote muscle growth by maintaining myoblasts in the proliferate state and delaying differentiation (increased Cdkn1c and Igf2, decreased Itg1bp3). A similar pattern of gene expression is observed in orchidectomized male mice, during androgen withdrawal-dependent muscle atrophy. In conclusion, androgens are not required for peak muscle mass in females. In males, androgens act through the AR to regulate multiple gene pathways that control muscle mass, strength, and fatigue resistance.
Internal ID Number: 18390925
URI: http://ahro.austin.org.au/austinjspui/handle/1/10582
DOI: 10.1096/fj.08-105726
URL: http://www.ncbi.nlm.nih.gov/pubmed/18390925
Type: Journal Article
Subjects: Androgens.physiology
Animals
Cell Differentiation
Cell Proliferation
Female
Gene Expression
Gene Regulatory Networks
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Muscle Contraction.physiology
Muscle Fibers, Fast-Twitch.physiology
Muscle Fibers, Slow-Twitch.physiology
Muscle, Skeletal.growth & development.pathology.physiopathology
Myoblasts, Skeletal.pathology.physiology
Orchiectomy
Organ Size
Receptors, Androgen.deficiency.genetics.physiology
Sex Characteristics
Testis.physiology
Appears in Collections:Journal articles

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