The effects of androstanolone (a synthetic DHT) on maximum isometric force in intact mouse skeletal muscle fibres

University of Cambridge (2008) Proc Physiol Soc 11, C56

Oral Communications: The effects of androstanolone (a synthetic DHT) on maximum isometric force in intact mouse skeletal muscle fibres

G. Mutungi1

1. Biomedical Research Centre, University of East Anglia, Norwich, United Kingdom.

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Although the chronic administration of testosterone and its derivatives to both animals and humans has been the subject of numerous previous studies (Kuhn, 2002) little is known about the acute actions of these compounds in isolated intact mammalian skeletal muscle fibres. Therefore, the main aim of this study was to investigate the rapid actions of androstanolone (a synthetic dihydrotestosterone; DHT) in intact mammalian skeletal muscle fibre bundles isolated from adult female CD1 mice. The mice were killed by dislocation of the neck followed by severing of the spinal cord and the extensor digitorum longus (edl, a mainly fast-twitch muscle) and the soleus (a predominantly slow-twitch muscle) were isolated. Small muscle fibre bundles (4-6 fibres – mean cross-sectional diameter ~120µm) were then dissected under dark-field illumination and mounted between two stainless steel hooks in a flow through muscle chamber. The experiments were performed at 20±0.1°C. The results show that treating muscle fibre bundles with physiological concentrations of androstanolone for only 30 minutes increases maximum isometric force (Po) in fast-twitch fibres but decreases it in slow-twitch fibres. Furthermore, in both fibre types these effects could be reversibly abolished by cycloheximide and cyproterone but they were relatively insensitive to actinomycin D and 10μM 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4,d]pyrimidine (PP2). Thus, 630ρgml-1 of androstanolone led to a 29.6±3% (n=8 fibre bundles) increase in Po in the fast-twitch fibres and to a 21.1±3% (n=7) decrease in Po in the slow-twitch fibres. From these results we suggest that androstanolone acts via the androgen receptor to increase the translation of a protein(s) that increases force production in fast-twitch skeletal muscle fibres but inhibits it in slow-twitch fibres.



Where applicable, experiments conform with Society ethical requirements.

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