Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway
Version of Record online: 17 SEP 2008
© 2008 The Authors. Journal compilation © 2008 Scandinavian Physiological Society
Volume 195, Issue 4, pages 471–482, April 2009
How to Cite
Hourdé, C., Jagerschmidt, C., Clément-Lacroix, P., Vignaud, A., Ammann, P., Butler-Browne, G. S. and Ferry, A. (2009), Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway. Acta Physiologica, 195: 471–482. doi: 10.1111/j.1748-1716.2008.01902.x
- Issue online: 6 MAR 2009
- Version of Record online: 17 SEP 2008
- Received 31 March 2008, revision requested 10 May 2008, final revision received 8 September 2008, accepted 12 September 2008
- Akt/mTor signalling;
- force production;
- hormone replacement therapy;
- skeletal muscle
Aim: We analysed the effect of physiological doses of androgens following orchidectomy on skeletal muscle and bone of male rats, as well as the relationships between muscle performance, hypertrophy and the Akt/mammalian target of rapamycin (mTOR) signalling pathway involved in the control of anabolic and catabolic muscle metabolism.
Methods: We studied the soleus muscle and tibia from intact rats (SHAM), orchidectomized rats treated for 3 months with vehicle (ORX), nandrolone decanoate (NAN) or dihydrotestosterone (DHT).
Results: Orchidectomy had very little effect on the soleus muscle. However, maximal force production by soleus muscle (+69%) and fatigue resistance (+35%) in NAN rats were both increased when compared with ORX rats. In contrast, DHT treatment did not improve muscle function. The relative number of muscle fibres expressing slow myosin heavy chain and citrate synthase activity were not different in NAN and ORX rats. Moreover, NAN and DHT treatments did not modify muscle weights and cross-sectional area of muscle fibres. Furthermore, phosphorylation levels of downstream targets of the Akt/mTOR signalling pathway, Akt, ribosomal protein S6 and eukaryotic initiation factor 4E-binding protein 1 were similar in muscles of NAN, DHT and ORX rats. In addition, trabecular tibia from NAN and DHT rats displayed higher bone mineral density and bone volume when compared with ORX rats. Only in NAN rats was this associated with increased bone resistance to fracture.
Conclusion: Physiological doses of androgens are beneficial to muscle performance in orchidectomized rats without relationship to muscle and fibre hypertrophy and activation of the Akt/mTOR signalling pathway. Taken together our data clearly indicate that the activity of androgens on muscle and bone could participate in the global improvement of musculoskeletal status in the context of androgen deprivation induced by ageing.