caa a22 4500 44585281X CHVBK 20180317145418.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s00204-010-0607-8 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0607-8 Myosin heavy chain expression pattern as a marker for anabolic potency: desoxymethyltestosterone (madol), norandrostendione and testosterone repress MHC-IIb expression and stimulate MHC-IId/x expression in orchiectomized rat gastrocnemius muscle [Elektronische Daten] [S. Frese, M. Velders, B. Schleipen, W. Schänzer, W. Bloch, P. Diel] Both 19-norandrostenedione (estr-4-ene-3,17-dione, NOR) and desoxymethyltestosterone (17alpha-methyl-5alpha-androst-2-en-17beta-ol, DMT or "madol”) are ‘designer steroids' misused for doping purposes in the bodybuilding scene. We have previously characterized the pharmacological profile of madol and identified potential adverse side effects. The aim of this study was to investigate the anabolic potency of NOR, madol and the reference substance testosterone propionate (TP). Besides wet weight of the M.levator ani (LA), we examined the effects on muscle fiber type composition and myosin heavy chain (MHC) expression in the M.gastrocnemius (Gas) muscle as additional markers for anabolic potency. A Hershberger assay was performed, where orchiectomized (orchi) male Wistar rats were treated subcutaneously with NOR, madol, TP or vehicle control (all 1mg/kgBW/day) for 12days. Wet weights of the Gas, LA, prostate and seminal vesicle were examined to determine anabolic and androgenic effects. Fiber type composition of the Gas muscle was analyzed using ATPase staining, and MHC protein profiles were determined by silver stain and Western blot analysis. NOR and madol exhibited strong anabolic and weak androgenic potency by stimulating growth of the LA but not the prostate and seminal vesicle. Skeletal muscle fiber type composition characterized by ATPase staining was not significantly altered between the treatment groups, although there was a tendency toward lower levels of type IIB and increased type IIA fibers in all treatment groups relative to orchi. MHC protein expression determined by Western blot and silver stain analysis revealed that MHC IId/x was significantly up-regulated, while MHC IIb was significantly down-regulated in NOR, madol and TP groups relative to orchi. There were no significant differences for MHC IIa and MHC I expression between groups. Results suggest that the observed MHC expression shift could serve as a molecular marker to determine anabolic activity of anabolic steroids at least in skeletal muscle of orchi rats. The molecular mechanisms as well as the androgen-dependent regulation of MHC expression in intact skeletal muscle remain to be further investigated. Springer-Verlag, 2010 Testosterone nationallicence Madol nationallicence Desoxymethyltestosterone nationallicence NORandrostendione nationallicence Skeletal muscle nationallicence Myosin heavy chain nationallicence Fiber type composition nationallicence Frese S. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut Velders M. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut Schleipen B. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut Schänzer W. Center for Preventive Doping Control, Institute of Biochemistry, German Sports University, Cologne, Germany aut Bloch W. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut Diel P. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 635-643 0340-5761 85:6<635 2011 85 204 https://doi.org/10.1007/s00204-010-0607-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0607-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Frese S. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut NATIONALLICENCE 700 1- Velders M. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut NATIONALLICENCE 700 1- Schleipen B. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut NATIONALLICENCE 700 1- Schänzer W. Center for Preventive Doping Control, Institute of Biochemistry, German Sports University, Cologne, Germany aut NATIONALLICENCE 700 1- Bloch W. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut NATIONALLICENCE 700 1- Diel P. Center for Preventive Doping Control, Institute of Sports Medicine, Department of Molecular and Cellular Sports Medicine, German Sports College of Köln, German Sports University, Carl Diem Weg 6, 50927, Cologne, Germany aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/6(2011-06-01), 635-643 0340-5761 85:6<635 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer