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Nemours Children’s Clinic, Jacksonville, Florida 32207; Divisions of Endocrinology (N.M., V.H., S.W., A.R.), Physical Therapy (K.H.), and Pediatric Surgery (M.D.), Department of Medicine (J.D.V.), University of Virginia Medical Center, Charlottesville, Virginia 22908; and the Department of Medicine (R.J.U.), University of Texas Medical Branch, Galveston, Texas 77555-1060
Address all correspondence and requests for reprints to: Nelly Mauras, M.D., Nemours Children’s Clinic, 807 Nira Street, Jacksonville, Florida 32207. E-mail: nmauras{at}nemours.org
To investigate specific effects of androgens on whole body metabolism, we studied six healthy lean men (mean ± SEM age, 23.2 ± 0.5 yr) before and after gonadal steroid suppression with a GnRH analog (Lupron), given twice, 3 weeks apart. Primed infusions of [13C]leucine, indirect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and after 10 weeks of treatment (D2); each subject served as his own control. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 ± 141 ng/dL; D2, 31 ± 9). Leucine’s rate of appearance (index of proteolysis) was markedly suppressed after 10 weeks of hypogonadism (-13%; P = 0.01) as well as the nonoxidative leucine disposal, an index of whole body protein synthesis (-13%; P = 0.01) without any changes in plasma amino acid concentrations. All subjects studied after 10 weeks showed a decrease in fat-free mass, as measured by skinfold calipers and dual emission x-ray absortiometry scans (D1, 56.5 ± 2.9 kg; D2, 54.4 ± 2.5; P = 0.005), and an increase in percent fat mass (D1, 19.2 ± 2.5%; D2, 22.2 ± 2.5; P = 0.001). Rates of lipid oxidation decreased (-31%; P = 0.05) after treatment, with parallel changes in resting energy expenditure (-9%; P = 0.05). Mean and peak GH concentrations (measured every 10 min for 6 h) and GH production rates did not decrease after testosterone deficiency, with an actual increase in basal secretion (P < 0.02). Plasma insulin-like growth factor I (IGF-I) concentrations did not change significantly after 10 weeks of treatment (D1, 227 ± 44 µg/L; D2, 291 ± 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60° and 180°/s was also decreased after 10 weeks of hypogonadism. Total ribonucleic acid (RNA) was isolated from muscle biopsy samples, and ribonuclease protection assays were performed using human complementary DNA clones for IGF-I, IGF-binding protein-4, myosin, and actin. Ten weeks after Lupron treatment, messenger RNA (mRNA) concentrations of IGF-I decreased significantly, whereas there was a trend toward higher IGF-binding protein-4 concentrations, with no change in myosin or actin mRNA concentrations.
In conclusion, testosterone deficiency in young men is associated with a marked decrease in measures of whole body protein anabolism, decreased strength, decreased fat oxidation, and increased adiposity. These effects of testosterone deficiency are independent of changes in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effect of androgens on whole body lipid and protein metabolism.
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S. Bhasin, L. Woodhouse, R. Casaburi, A. B. Singh, D. Bhasin, N. Berman, X. Chen, K. E. Yarasheski, L. Magliano, C. Dzekov, et al. Testosterone dose-response relationships in healthy young men Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1172 - E1181. [Abstract] [Full Text] [PDF]
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S. Basaria, J. T. Wahlstrom, and A. S. Dobs Anabolic-Androgenic Steroid Therapy in the Treatment of Chronic Diseases J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5108 - 5117. [Abstract] [Full Text] [PDF]
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R. J. Saad, B. S. Keenan, K. Danadian, V. D. Lewy, and S. A. Arslanian Dihydrotestosterone Treatment in Adolescents with Delayed Puberty: Does it Explain Insulin Resistance of Puberty? J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4881 - 4886. [Abstract] [Full Text] [PDF]
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P. J. Snyder Effects of Age on Testicular Function and Consequences of Testosterone Treatment J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2369 - 2372. [Full Text] [PDF]
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V. Y. Hayes, R. J. Urban, J. Jiang, T. J. Marcell, K. Helgeson, and N. Mauras Recombinant Human Growth Hormone and Recombinant Human Insulin-Like Growth Factor I Diminish the Catabolic Effects of Hypogonadism in Man: Metabolic and Molecular Effects J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2211 - 2219. [Abstract] [Full Text]
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M. M. Bamman, J. R. Shipp, J. Jiang, B. A. Gower, G. R. Hunter, A. Goodman, C. L. McLafferty Jr., and R. J. Urban Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans Am J Physiol Endocrinol Metab, March 1, 2001; 280(3): E383 - E390. [Abstract] [Full Text] [PDF]
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S. M. Harman, E. J. Metter, J. D. Tobin, J. Pearson, and M. R. Blackman Longitudinal Effects of Aging on Serum Total and Free Testosterone Levels in Healthy Men J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 724 - 731. [Abstract] [Full Text]
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B. A. Gower and L. Nyman Associations among Oral Estrogen Use, Free Testosterone Concentration, and Lean Body Mass among Postmenopausal Women J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4476 - 4480. [Abstract] [Full Text]
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N. Mauras, V. Martinez, A. Rini, and J. Guevara-Aguirre Recombinant Human Insulin-Like Growth Factor I Has Significant Anabolic Effects in Adults with Growth Hormone Receptor Deficiency: Studies on Protein, Glucose, and Lipid Metabolism J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3036 - 3042. [Abstract] [Full Text]
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P. J. Snyder, H. Peachey, J. A. Berlin, P. Hannoush, G. Haddad, A. Dlewati, J. Santanna, L. Loh, D. A. Lenrow, J. H. Holmes, et al. Effects of Testosterone Replacement in Hypogonadal Men J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2670 - 2677. [Abstract] [Full Text]
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N. Mauras, K. O. O’Brien, K. O. Klein, and V. Hayes Estrogen Suppression in Males: Metabolic Effects J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2370 - 2377. [Abstract] [Full Text]
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N. Mauras, K. O. O’Brien, S. Welch, A. Rini, K. Helgeson, N. E. Vieira, and A. L. Yergey Insulin-Like Growth Factor I and Growth Hormone (GH) Treatment in GH-Deficient Humans: Differential Effects on Protein, Glucose, Lipid, and Calcium Metabolism J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1686 - 1694. [Abstract] [Full Text]
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Is Obesity an Outcome of Gonadotropin-Releasing Hormone Agonist Administration? Analysis of Growth and Body Composition in 110 Patients with Central Precocious Puberty J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4480 - 4488. [Abstract] [Full Text]
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P. J. Snyder, H. Peachey, P. Hannoush, J. A. Berlin, L. Loh, D. A. Lenrow, J. H. Holmes, A. Dlewati, J. Santanna, C. J. Rosen, et al. Effect of Testosterone Treatment on Body Composition and Muscle Strength in Men Over 65 Years of Age J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2647 - 2653. [Abstract] [Full Text]
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M. Sheffield-Moore, R. J. Urban, S. E. Wolf, J. Jiang, D. H. Catlin, D. N. Herndon, R. R. Wolfe, and A. A. Ferrando Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2705 - 2711. [Abstract] [Full Text]
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A. Giustina and J. D. Veldhuis Pathophysiology of the Neuroregulation of Growth Hormone Secretion in Experimental Animals and the Human Endocr. Rev., December 1, 1998; 19(6): 717 - 797. [Abstract] [Full Text]
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M. I. Lewis, G. D. Horvitz, D. R. Clemmons, and M. Fournier Role of IGF-I and IGF-binding proteins within diaphragm muscle in modulating the effects of nandrolone Am J Physiol Endocrinol Metab, February 1, 2002; 282(2): E483 - E490. [Abstract] [Full Text] [PDF]
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A. A. Ferrando, M. Sheffield-Moore, C. W. Yeckel, C. Gilkison, J. Jiang, A. Achacosa, S. A. Lieberman, K. Tipton, R. R. Wolfe, and R. J. Urban Testosterone administration to older men improves muscle function: molecular and physiological mechanisms Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E601 - E607. [Abstract] [Full Text] [PDF]
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