title: The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle.
abstract: Testosterone (T) supplementation increases skeletal muscle mass, circulating GH, IGF-I, and im IGF-I expression, but the role of GH and IGF-I in mediating T's effects on the skeletal muscle remains poorly understood. Here, we show that T administration increased body weight and the mass of the androgen-dependent levator ani muscle in hypophysectomized as well as castrated plus hypophysectomized adult male rats. T stimulated the proliferation of primary human skeletal muscle cells (hSKMCs) in vitro, an effect blocked by transfecting hSKMCs with small interference RNA targeting human IGF-I receptor (IGF-IR). In differentiation conditions, T promoted the fusion of hSKMCs into larger myotubes, an effect attenuated by small interference RNA targeting human IGF-IR. Notably, MKR mice, which express a dominant negative form of the IGF-IR in skeletal muscle fibers, treated with a GnRH antagonist (acyline) to suppress endogenous T, responded to T administration by an attenuated increase in the levator ani muscle mass. In conclusion, circulating GH and IGF-I are not essential for mediating T's effects on an androgen-responsive skeletal muscle. IGF-I signaling plays an important role in mediating T's effects on skeletal muscle progenitor cell growth and differentiation in vitro. However, IGF-IR signaling in skeletal muscle fibers does not appear to be obligatory for mediating the anabolic effects of T on the mass of androgen-responsive skeletal muscles in mice.
authors.affiliation: Section of Endocrinology, Diabetes, and Nutrition, Boston Medical Center, 670 Albany Street, Boston, Massachusetts 02118, USA. cserra@bu.edu
authors.forename: Carlo
authors.initials: C
authors.lastname: Serra
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Frances
authors.initials: F
authors.lastname: Tangherlini
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Barton
authors.forename: Michelle
authors.initials: M
authors.lastname: Ganno
authors.forename: Anqi
authors.initials: A
authors.lastname: Zhang
authors.forename: Janet
authors.initials: J
authors.lastname: Shansky
authors.forename: Herman H
authors.initials: HH
authors.lastname: Vandenburgh
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Travison
authors.forename: Ravi
authors.initials: R
authors.lastname: Jasuja
authors.forename: Carl
authors.initials: C
authors.lastname: Morris
mesh_terms: D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009919:Orchiectomy; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D034741:RNA, Small Interfering; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1