Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC71
Dihydrotestosterone (DHT) increases the uptake of isoleucine in mouse fast-twitch fibre bundles through an epidermal growth factor receptor (EGFR)-dependent mechanism
G. Mutungi1, M. M. Hamdi1
1. Biomedical and Clinical Sciences Research Institute, University of East Anglia, Norwich, United Kingdom.
In a recent study we showed that DHT increases twitch and tetanic tension in fast-twitch fibres but decreases them in slow-twitch fibres. These effects were mediated through the epidermal growth factor receptor (EGFR) and involved activation of the mitogen-activated protein kinase (MAPK) pathway (Hamdi and Mutungi, 2010). However, whether activation of this pathway has other physiological functions in mammalian skeletal muscle is uncertain. Therefore, the primary aim of this study was to investigate the acute effects of DHT on amino acid uptake in mouse skeletal muscle fibres. The experiments were performed at 20 ± 0.1°C using small fibre bundles isolated from the edl and soleus of adult female mice. The animals were humanely killed and all the experiments conformed to the Animals (Scientific Procedures) Act, 1986. The bundles were treated with Ringer’s solution containing 630ρgml-1 of ethanol (controls) or DHT/testosterone (T) plus carbon-14 labelled isoleucine [2mM, IL-U14C] for 1hr. Pharmacological interventions were then used to investigate the mechanism underlying the effects of DHT and T on IL-U14C uptake. DHT led to a 188.65 ± 7.47% (n=4) increase in the uptake of IL-U14C in fast-twitch fibres only. In contrast, testosterone had no effect on IL-U14C uptake in both fibre types. The DHT-induced increase in IL-U14C uptake was blocked by AG1478, PD98059, cycloheximide and actinomycin D. However, it was relatively insensitive to cyproterone and flutamide. From these results we suggest that DHT increases amino acid uptake in mammalian skeletal muscle fibres and this may have implications on muscle hypertrophy.
Where applicable, experiments conform with Society ethical requirements