Antonio J, Wilson JD, George FW. Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles. J Appl Physiol 1999;87(6):2016-9. http://jap.physiology.org/content/87/6/2016.long (Effects of castration and androgen treatment on androgen-receptor levels in rat skeletal muscles)
The effects of castration and dihydrotestosterone (DHT) treatment on levels of skeletal muscle androgen receptor (AR) were examined in three groups of adult male rats: 1) intact normal rats, 2) rats castrated at 16 wk of age, and 3) rats castrated at 16 wk of age and given DHT for 1 wk starting at week 17. All animals were killed at 18 wk of age.
Castration caused a decrease (P < 0.05) in the weights of the levator ani and bulbocavernosus muscles. The administration of DHT to the castrated rats increased (P < 0.05) the weights of the levator ani and bulbocavernosus muscles.
Castration caused a significant downregulation of AR levels in the bulbocavernosus (P < 0.05) but had no significant effect on AR levels in the levator ani muscle. DHT administration to the castrated group upregulated AR levels in the bulbocavernosus and levator ani muscles. The plantaris muscle did not significantly (P > 0.05) change for any of the treatments. These findings suggest that the effects of castration and androgen replacement differentially affect skeletal muscle mass and AR levels.
Sinha-Hikim I, Taylor WE, Gonzalez-Cadavid NF, Zheng W, Bhasin S. Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment. Journal of Clinical Endocrinology & Metabolism 2004;89(10):5245-55. http://jcem.endojournals.org/content/89/10/5245.full (Androgen Receptor in Human Skeletal Muscle and Cultured Muscle Satellite Cells: Up-Regulation by Androgen Treatment)
Androgens stimulate myogenesis, but we do not know what cell types within human skeletal muscle express the androgen receptor (AR) protein and are the target of androgen action. Because testosterone promotes the commitment of pluripotent, mesenchymal cells into myogenic lineage, we hypothesized that AR would be expressed in mesenchymal precursor cells in the skeletal muscle. AR expression was evaluated by immunohistochemical staining, confocal immunofluorescence, and immunoelectron microscopy in sections of vastus lateralis from healthy men before and after treatment with a supraphysiological dose of testosterone enanthate. Satellite cell cultures from human skeletal muscle were also tested for AR expression.
AR protein was expressed predominantly in satellite cells, identified by their location outside sarcolemma and inside basal lamina, and by CD34 and C-met staining. Many myonuclei in muscle fibers also demonstrated AR immunostaining. Additionally, CD34+ stem cells in the interstitium, fibroblasts, and mast cells expressed AR immunoreactivity. AR expression was also observed in vascular endothelial and smooth muscle cells. Immunoelectron microscopy revealed aggregation of immunogold particles in nucleoli of satellite cells and myonuclei; testosterone treatment increased nucleolar AR density. In enriched cultures of human satellite cells, more than 95% of cells stained for CD34 and C-met, confirming their identity as satellite cells, and expressed AR protein. AR mRNA and protein expression in satellite cell cultures was confirmed by RT-PCR, reverse transcription and real-time PCR, sequencing of RT-PCR product, and Western blot analysis.
Incubation of satellite cell cultures with supraphysiological testosterone and dihydrotestosterone concentrations (100 nm testosterone and 30 nm dihydrotestosterone) modestly increased AR protein levels. We conclude that AR is expressed in several cell types in human skeletal muscle, including satellite cells, fibroblasts, CD34+ precursor cells, vascular endothelial, smooth muscle cells, and mast cells. Satellite cells are the predominant site of AR expression.
These observations support the hypothesis that androgens increase muscle mass in part by acting on several cell types to regulate the differentiation of mesenchymal precursor cells in the skeletal muscle.
Carson JA, Lee WJ, McClung J, Hand GA. Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration. Journal of Applied Physiology 2002;93(1):242-50. http://jap.physiology.org/content/93/1/242.full (Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration)
Skeletal muscle is a target of anabolic steroid action; however, anabolic steroid's affect on aged skeletal muscle is not well understood. The effect of 4 wk of nandrolone decanoate (ND) administration on hindlimb muscles of 5- and 25-mo-old Fischer 344/Brown Norway rats was examined. ND (6 mg/kg body wt) was injected every 7th day for 4 wk. Controls received an oil injection. ND significantly reduced 25-mo-old rat perirenal fat pad mass by 30%. Soleus (Sol) and plantaris (Plan) muscle-to-body weight ratios were reduced in 25-mo-old rats. ND did not affect Sol or Plan muscle-to-body weight ratios at either age. Sol DNA concentration was reduced by 25% in 25-mo-old rats, and ND increased it to 12% greater than 5-mo-old rats. ND did not affect Plan DNA content. Sol androgen receptor (AR) protein in 25-mo-old rats was reduced to 35% of 5-mo-old values. ND increased AR protein by 900% in 25-mo-old rat Sol. Plan AR concentration was not affected by aging but was induced by ND in both age groups. Aging or ND treatment did not affect glucocorticoid receptor levels in either muscle. These data demonstrate that fast- and slow-twitch rat hindlimb muscles differ in their response to aging and ND therapy.