Myostatin protein and muscle fiber cross-sectional area are associated with increased muscle satellite cell number in 10 month old fisher 344 rats treated with testosterone and trenbolone enanthate

Influence of 5α-reductase and/or aromatase enzymes on androgen-induced skeletal muscle maintenance in older adults is not fully elucidated. Our purpose was to determine the androgen-induced alterations in adult rodent skeletal muscle fiber cross sectional area (fCSA), satellite cell content, and myostatin (Mstn) signaling by comparing the effects of testosterone (TEST) versus trenbolone (TREN, a non-5α-reducible, non-aromatizable synthetic TEST analogue) in 10 month old Fisher 344 rats (n=41) randomly assigned to receive Sham surgery, orchiectomy (ORX), ORX+TEST (7.0 mg/week), or ORX+TREN (1.0 mg/week). After 29 days animals were euthanized and the levator ani/bulbocavernosus (LABC) muscle complex was weighed and preserved for analyses. LABC muscle fCSA after ORX was 37% lower than SHAM and ~50% lower than ORX+TEST and ORX+TREN (p<0.01). LABC fCSA was 28% higher in ORX+TEST compared to SHAM (p=0.012). ORX+TEST and ORX+TREN increased satellite cell numbers compared to SHAM and ORX (p<0.05), with no differences between conditions for myonuclear number per muscle fiber (p=0.948). Mstn protein was increased roughly 3-fold in the ORX+TEST and ORX+TREN groups versus Sham and ORX groups (p<0.01). Mstn mRNA, was lower in ORX, ORX+TEST and ORX+TREN compared to SHAM (p<0.05). Muscle fCSA was highly positively correlated with muscle satellite cell number (r = 0.730, p < 0.001). Mature Mstn protein was positively correlated with muscle satellite cell number (r = 0.430, p = 0.008). TEST and TREN increased muscle fCSA and satellite cell number without increasing myonuclei number, and increased Mstn protein levels. Mstn protein and Muscle fCSA were associated with increased muscle satellite cell number. TEST and TREN appear to up-regulate Mstn protein levels to prevent uncontrolled muscle growth in older animals. In addition, the similar effects of TEST and TREN observed in the current study suggest the action of 5α-reductase and/or aromatase enzymes are inconsequential for the androgenic maintenance of skeletal muscle in older adult males.