Testosterone effects on muscle histomorphometry

In order to determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy or hyperplasia, muscle biopsies were obtained from vastus lateralis in 39 men before and after 20 weeks of combined treatment with GnRH agonist and weekly injections of 25, 50, 125, 300 or 600 mg testosterone enanthate (Sinha-Hikim et al. 2002). Changes in cross-sectional areas of both type I and II fibers were dependent on testosterone dose, and significantly correlated with total (r = 0.35, and 0.44, P < 0.0001 for type I and II fibers, respectively) and free (r = 0.34 and 0.35, P < 0.005) testosterone concentrations during treatment (Fig. 8.2). The men receiving 300 and 600 mg of testosterone enanthate weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wks, 3176 ± 163 vs. 4201 ± 163 ^m2, P < 0.05 at 300-mg dose, and 3347 ± 253 vs. 4984 ± 374 ^m2, P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional areas of

Changes in Myonuclear and Satellite Cell Number After Treatment with GnRH Agonist and Testosterone

16 i

Myonuclei Number/mm 8 -i

300 mg

600 mg

125 mg Satellite Cell Number/mm

300 mg

600 mg

Testosterone Enanthate Dose Levels

Fig. 8.3 The effect of testosterone administration on myonuclear number and absolute satellite cell number

The number of myonuclei (upper panel) and satellite cells per mm of muscle fiber length (middle panel) were computed by spatial distribution. Change was calculated as the difference between post-treatment and baseline values. Values significantly different from zero are marked by asterisks. The weekly dose of testosterone enanthate is shown at the bottom. *, P = 0.04 vs. zero change; **, P =0.03 vs. zero change. (Reproduced with permission from Sinha-Hikim etal. 2003.)

type II (4060 ± 401 vs. 5526 ± 544 ^m2, P = 0.03) fibers. The relative proportions of type I and type II fibers did not change significantly after treatment in any group. The myonuclear number per fiber increased significantly in men receiving the 300 and 600 mg doses of testosterone enanthate, and was significantly correlated with testosterone concentration, and muscle fiber cross-sectional area (Sinha-Hikim etal. 2002).

These data demonstrate that increases in muscle volume in healthy eugonadal men treated with graded doses of testosterone are associated with concentration-dependent increases in muscle fiber cross-sectional area and myonulcear number, but not muscle fiber number. We conclude that the testosterone-induced increase in muscle volume is due to muscle fiber hypertrophy. Testosterone-induced muscle fiber hypertrophy was also associated with an increase in satellite cell number and a proportionate increase in myonuclear number (Fig. 8.3) (Sinha-Hikim etal. 2002). The mechanisms by which testosterone might increase satellite cell number are not known. An increase in satellite cell number could occur by an increase in satellite cell replication, inhibition of satellite cell apoptosis, and/or increased differentiation of stem cells into the myogenic lineage. We do not know which of these processes is the site of regulation by testosterone.

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