title: Selective androgen receptor modulator, YK11, regulates myogenic differentiation of C2C12 myoblasts by follistatin expression.
abstract: The myogenic differentiation of C2C12 myoblast cells is induced by the novel androgen receptor (AR) partial agonist, (17α,20E)-17,20-[(1-methoxyethylidene)bis-(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester (YK11), as well as by dihydrotestosterone (DHT). YK11 is a selective androgen receptor modulator (SARM), which activates AR without the N/C interaction. In this study, we further investigated the mechanism by which YK11 induces myogenic differentiation of C2C12 cells. The induction of key myogenic regulatory factors (MRFs), such as myogenic differentiation factor (MyoD), myogenic factor 5 (Myf5) and myogenin, was more significant in the presence of YK11 than in the presence of DHT. YK11 treatment of C2C12 cells, but not DHT, induced the expression of follistatin (Fst), and the YK11-mediated myogenic differentiation was reversed by anti-Fst antibody. These results suggest that the induction of Fst is important for the anabolic effect of YK11.
authors.affiliation: Faculty of Pharmaceutical Sciences, Toho University.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Kanno
authors.forename: Rumi
authors.initials: R
authors.lastname: Ota
authors.forename: Kousuke
authors.initials: K
authors.lastname: Someya
authors.forename: Taichi
authors.initials: T
authors.lastname: Kusakabe
authors.forename: Keisuke
authors.initials: K
authors.lastname: Kato
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Inouye
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005485:Flutamide / Q000031:analogs & derivatives / Q000494:pharmacology; D038681:Follistatin / Q000235:genetics*; D051379:Mice; D017570:MyoD Protein / Q000235:genetics; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics; D018008:Myogenin / Q000235:genetics; D009649:Norpregnadienes / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: C562327:17,20-((1-methoxyethylidene)bis(oxy))-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester; D000726:Androgen Antagonists; D000728:Androgens; D038681:Follistatin; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018008:Myogenin; D009649:Norpregnadienes; D012333:RNA, Messenger; D011944:Receptors, Androgen; C014290:hydroxyflutamide; D005485:Flutamide