PMID- 18801052 OWN - NLM STAT- MEDLINE DCOM- 20100415 LR - 20211203 IS - 1748-1716 (Electronic) IS - 1748-1708 (Linking) VI - 195 IP - 4 DP - 2009 Apr TI - Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway. PG - 471-82 LID - 10.1111/j.1748-1716.2008.01902.x [doi] AB - 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. FAU - Hourde, C AU - Hourde C AD - INSERM, Paris, France. FAU - Jagerschmidt, C AU - Jagerschmidt C FAU - Clement-Lacroix, P AU - Clement-Lacroix P FAU - Vignaud, A AU - Vignaud A FAU - Ammann, P AU - Ammann P FAU - Butler-Browne, G S AU - Butler-Browne GS FAU - Ferry, A AU - Ferry A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20081013 PL - England TA - Acta Physiol (Oxf) JT - Acta physiologica (Oxford, England) JID - 101262545 RN - 0 (Anabolic Agents) RN - 0 (Androgens) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 08J2K08A3Y (Dihydrotestosterone) RN - 6PG9VR430D (Nandrolone) RN - EC 2.3.3.1 (Citrate (si)-Synthase) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Oncogene Protein v-akt) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - EC 3.6.4.1 (Myosin Heavy Chains) RN - H45187T098 (Nandrolone Decanoate) SB - IM MH - Anabolic Agents/therapeutic use MH - Androgens/*therapeutic use MH - Animals MH - Bone Density/drug effects MH - Citrate (si)-Synthase/metabolism MH - Dihydrotestosterone/therapeutic use MH - *Hormone Replacement Therapy MH - Hypertrophy MH - Intracellular Signaling Peptides and Proteins/*metabolism MH - Male MH - Muscle, Skeletal/*drug effects/*pathology/physiopathology MH - Muscular Diseases/*drug therapy/*physiopathology MH - Myosin Heavy Chains/metabolism MH - Nandrolone/analogs & derivatives/therapeutic use MH - Nandrolone Decanoate MH - Oncogene Protein v-akt/*metabolism MH - Orchiectomy MH - Protein Serine-Threonine Kinases/*metabolism MH - Rats MH - TOR Serine-Threonine Kinases MH - Tibia/drug effects/metabolism/pathology EDAT- 2008/09/20 09:00 MHDA- 2010/04/16 06:00 CRDT- 2008/09/20 09:00 PHST- 2008/09/20 09:00 [pubmed] PHST- 2010/04/16 06:00 [medline] PHST- 2008/09/20 09:00 [entrez] AID - APS1902 [pii] AID - 10.1111/j.1748-1716.2008.01902.x [doi] PST - ppublish SO - Acta Physiol (Oxf). 2009 Apr;195(4):471-82. doi: 10.1111/j.1748-1716.2008.01902.x. Epub 2008 Oct 13.