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Articles in PresS, published online ahead of print March 12, 2002
Am J Physiol Endocrinol Metab, 10.1152/ajpendo.00502.2001
Submitted on November 7, 2001
Accepted on March 10, 2002
1 Endocrinology, Metabolism, and Molecular Medicine, Charles Drew University, Los Angeles, CA, USA
2 Division of Respiratory and Critical Caree Physiology and Medicine, Harbor-UCLA Medical Center, Torrance, CA, USA
* To whom correspondence should be addressed. E-mail: sbhasin{at}ucla.edu.
Administration of replacement doses of testosterone to healthy hypogonadal men and supraphysiologic doses to eugonadal men increases muscle size. In order to determine whether testosterone-induced increase in muscle size is due to muscle fiber hypertrophy or hyperplasia, 61 healthy men, 18-35 years of age, received monthly injections of a long acting GnRH agonist to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300 or 600-mg testosterone enanthate (TE) for 20 weeks. Thigh muscle volume was measured by magnetic resonance imaging (MRI) scan, and muscle biopsies were obtained from vastus lateralis in 39 men before and after 20-weeks of combined treatment with GnRH agonist and testosterone. Administration of GnRH agonist plus TE resulted in mean nadir testosterone concentrations of 234, 289, 695, 1344, and 2,435 ng/dL at the 25, 50, 125, 300, and 600 mg doses, respectively. Graded doses of testosterone administration were associated with testosterone dose and concentration-dependent increase in muscle volume measured by MRI (changes in vastus lateralis volume, -4, +7, +15, +32, and +48 cc at 25, 50, 125, 300, and 600 mg doses, respectively). 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. The men receiving 300 and 600 mg of TE weekly experienced significant increases from baseline in areas of type I (baseline vs. 20 wks, 3176±186 vs. 4201±252 µm2, P<0.05 at 300-mg dose, and 3347 ± 253 vs. 4984 ± 374 µm2, P = 0.006 at 600-mg dose) muscle fibers; the men in the 600-mg group also had significant increments in cross-sectional area of type II (4060 ± 401 vs. 5526 ± 544 µm2, 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. Conclusion: The 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 areas of both type I and type II muscle fibers, and myonulcear number, but not muscle fiber number. We conclude that the testosterone induced increase in muscle volume is due to muscle fiber hypertrophy.
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