title: Phosphorylation of p70s6 kinase is implicated in androgen-induced levator ani muscle anabolism in castrated rats.
abstract: Androgens are known to increase muscle mass, strength and muscle protein synthesis. However, the molecular mechanisms by which androgens regulate skeletal muscle development remain poorly understood. The ribosomal protein kinase p70(s6k) is a regulator of ribosome biogenesis and plays an important role in the regulation of growth-related protein synthesis. The phosphorylation of p70(s6k) has been implicated in load-induced skeletal muscle hypertrophy. In the current study, we determined the effect of DHT on the phosphorylation of p70(s6k) in the androgen-sensitive levator ani muscle of castrated rats. DHT induced a rapid increase in the phosphorylation of p70(s6k), which was detectable within 6 h after a single injection. Interestingly, DHT-induced phosphorylation of p70(s6k) occurred only in androgen-sensitive muscles, but not prostate and seminal vesicle. Co-administration of flutamide, an AR antagonist, inhibited DHT-induced p70(s6k) phosphorylation. While serum IGF-I levels were not changed by DHT treatment, IGF-I gene expression levels increased and the mRNA levels of IGFBP3 and IGFBP5 were suppressed in the LA muscle after DHT replacement in castrated rats. These results suggest that the phosphorylation of p70(s6k), likely via the IGF-I pathway, may play an important role in androgen-induced skeletal muscle hypertrophy.
authors.affiliation: Department of Molecular Pharmacology, MV CEDD, GlaxoSmithKline Research and Development, RTP, NC 27709, USA. tianshun.s.xu@gsk.com
authors.forename: Tianshun
authors.initials: T
authors.lastname: Xu
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.forename: Heather
authors.initials: H
authors.lastname: Pink
authors.forename: Jim
authors.initials: J
authors.lastname: Triantafillou
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Stimpson
authors.forename: Philip
authors.initials: P
authors.lastname: Turnbull
authors.forename: Bajin
authors.initials: B
authors.lastname: Han
mesh_terms: D059002:Androgen Receptor Antagonists; D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*
chemical_list: D059002:Androgen Receptor Antagonists; D000728:Androgens; D018969:Insulin-Like Growth Factor Binding Proteins; D011944:Receptors, Androgen; D007334:Insulin-Like Growth Factor I; D038762:Ribosomal Protein S6 Kinases, 70-kDa