TESTOSTERONE DEFICIENCY IN YOUNG MEN - MARKED ALTERATIONS IN WHOLE-BODY PROTEIN KINETICS, STRENGTH, AND ADIPOSITY

To investigate specific effects of androgens on whole body metabolism, me studied six healthy lean men (mean +/- SEM age, 23.2 +/- 0.5 yr) b efore and after gonadal steroid suppression with a GnRH analog (Lupron ), given twice, 3 weeks apart. Primed infusions of [C-13]leucine, indi rect calorimetry, isokinetic dynamometry, growth factor measurements, and percutaneous muscle biopsies were performed at baseline (D1) and a fter 10 weeks of treatment (D2); each subject served as his own contro l. Testosterone concentrations were markedly suppressed after 10 weeks of treatment (D1, 535 +/- 141 ng/dL; D2, 31 +/- 9). Leucine's rate of appearance tinder of proteolysis) was markedly suppressed after 10 we eks of hypogonadism (-13%; P = 0.01) as well as the nonoxidative leuci ne 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 measure d 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 pe rcent 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 p arallel changes in resting energy expenditure (-9%; P = 0.05). Mean an d peak GH concentrations (measured every 10 min for 6 h) and GH produc tion rates did not decrease after testosterone deficiency, with an act ual 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 mu g/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 L upron treatment, messenger RNA (mRNA) concentrations of IGF-I decrease d significantly, whereas there was a trend toward higher IGF-binding p rotein-4 concentrations, with no change in myosin or actin mRNA concen trations. In conclusion, testosterone deficiency in young men is assoc iated with a marked decrease in measures of whole body protein anaboli sm, decreased strength, decreased fat oxidation, and increased adiposi ty. These effects of testosterone deficiency are independent of change s in peripheral GH production and IGF-I concentrations, even though im IGF-I mRNA concentrations decrease. These data suggest a direct effec t of androgens on whole body lipid and protein metabolism.