title: Muscle-specific androgen receptor deletion shows limited actions in myoblasts but not in myofibers in different muscles in vivo.
abstract: The aim of this study was to investigate the direct muscle cell-mediated actions of androgens by comparing two different mouse lines. The cre-loxP system was used to delete the DNA-binding activity of the androgen receptor (AR) in mature myofibers (MCK mAR(ΔZF2)) in one model and the DNA-binding activity of the AR in both proliferating myoblasts and myofibers (α-actin mAR(ΔZF2)) in another model. We found that hind-limb muscle mass was normal in MCK mAR(ΔZF2) mice and that relative mass of only some hind-limb muscles was reduced in α-actin mAR(ΔZF2) mice. This suggests that myoblasts and myofibers are not the major cellular targets mediating the anabolic actions of androgens on male muscle during growth and development. Levator ani muscle mass was decreased in both mouse lines, demonstrating that there is a myofiber-specific effect in this unique androgen-dependent muscle. We found that the pattern of expression of genes including c-myc, Fzd4 and Igf2 is associated with androgen-dependent changes in muscle mass; therefore, these genes are likely to be mediators of anabolic actions of androgens. Further research is required to identify the major targets of androgen actions in muscle, which are likely to include indirect actions via other tissues.
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia krana@unimelb.edu.au.
authors.forename: Kesha
authors.initials: K
authors.lastname: Rana
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Maria W S
authors.initials: MW
authors.lastname: Chiu
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Russell
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Jarrod P
authors.initials: JP
authors.lastname: Skinner
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Nicole K L
authors.initials: NK
authors.lastname: Lee
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Fam
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Zajac
authors.affiliation: Department of MedicineUniversity of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: MacLean
mesh_terms: D000818:Animals; D015415:Biomarkers; D017353:Gene Deletion; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D009929:Organ Size; D009928:Organ Specificity / Q000235:genetics; D010805:Physical Conditioning, Animal; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D018006:Myogenic Regulatory Factors; D011944:Receptors, Androgen
keywords: androgen receptor; muscle; myoblasts; myofibers