Testosterone Deficiency in Young Men: Marked Alterations in Whole Body Protein Kinetics, Strength, and Adiposity¹

Abstract

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 micrograms/L; D2, 291 +/- 60; P = 0.08). Isokinetic dynamometry of leg extensors at 60 degrees and 180 degrees/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.

The Acute Hormonal Response to the Kettlebell Swing Exercise

“…Testosterone is a potent anabolic-androgenic hormone, which, among other biological effects, stimulates muscle protein synthesis and inhibits protein degradation (Demling & Orgill, 2000;Mauras et al, 1998). Testosterone deficiency in young men has been associated with decreased strength (Mauras et al, 1998) and reductions in strength outcomes from resistance training (Kvorning et al, 2006), while supraphysiologic doses of T have been associated with increased muscle strength and hypertrophy (Bhasin et al, 1996).…”

“…Testosterone deficiency in young men has been associated with decreased strength (Mauras et al, 1998) and reductions in strength outcomes from resistance training (Kvorning et al, 2006), while supraphysiologic doses of T have been associated with increased muscle strength and hypertrophy (Bhasin et al, 1996). Serum T concentrations increase acutely in men following resistance exercise of sufficient intensity and volume.…”

Recruitment of the Androgen Receptor via Serum Response Factor Facilitates Expression of a Myogenic Gene

“…For example, men made hypogonadal lose lean body mass and muscle strength (1), whereas in older men, decrements in circulating testosterone levels correlates well with reduced musculature (2). In addition, treatment of hypogonadal men or older men with androgens elicited increased muscle strength and lean body mass (3,4).…”

Sarcopenia and Androgens: A Link between Pathology and Treatment

“…Figure 1 shows the relationship between androgen levels and the development of sarcopenia. Androgen supplementation has been observed to exert anabolic actions that enhance muscle strength and increase muscle size clinically (27)(28)(29)(30)(31). Although the biological mechanisms underlying androgen action in skeletal muscle remain poorly understood, muscle mass has been observed to be regulated by the normal balance between synthesis and degradation of muscle proteins, a mechanism that is regulated by various systemic hormones.…”