Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway

• Published in: Acta Physiologica Vol. 195; no. 4; pp. 471 - 482
• Main Authors: Hourdé, C., Jagerschmidt, C., Clément-Lacroix, P., Vignaud, A., Ammann, P., Butler-Browne, G. S., Ferry, A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-04-2009; Wiley-Blackwell
• Subjects: ageing; Akt/mTor signalling; Anabolic Agents - therapeutic use; androgen; Androgens - therapeutic use; Animals; Biological and medical sciences; Bone Density - drug effects; Citrate (si)-Synthase - metabolism; Dihydrotestosterone - therapeutic use; force production; Fundamental and applied biological sciences. Psychology; Hormone Replacement Therapy; Hypertrophy; Intracellular Signaling Peptides and Proteins - metabolism; Male; Muscle, Skeletal - drug effects; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Muscular Diseases - drug therapy; Muscular Diseases - physiopathology; Myosin Heavy Chains - metabolism; Nandrolone - analogs & derivatives; Nandrolone - therapeutic use; Oncogene Protein v-akt - metabolism; Orchiectomy; Protein-Serine-Threonine Kinases - metabolism; Rats; skeletal muscle; Tibia - drug effects; Tibia - metabolism; Tibia - pathology; TOR Serine-Threonine Kinases; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Senescence; Androgen; Rat; Force; Ageing; Rodentia; Male; Activation; Striated muscle; Vertebrata; Mammalia; force production; Hormone replacement therapy; Sex steroid hormone; skeletal muscle; Akt/mTor signalling; Hypertrophy
• ISSN: 1748-1708; 1748-1716
• DOI: 10.1111/j.1748-1716.2008.01902.x

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.