. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 282: E601-E607, 2002. First published November 13; 10.1152/ajpendo.00362.2001.-We investigated the effects of 6 mo of near-physiological testosterone administration to older men on skeletal muscle function and muscle protein metabolism. Twelve older men (Ն60 yr) with serum total testosterone concentrations Ͻ17 nmol/l (480 ng/dl) were randomly assigned in double-blind manner to receive either placebo (n ϭ 5) or testosterone enanthate (TE; n ϭ 7) injections. Weekly intramuscular injections were given for the 1st mo to establish increased blood testosterone concentrations at 1 mo and then changed to biweekly injections until the 6-mo time point. TE doses were adjusted to maintain nadir serum testosterone concentrations between 17 and 28 nmol/l. Lean body mass (LBM), muscle volume, prostate size, and urinary flow were measured at baseline and at 6 mo. Protein expression of androgen receptor (AR) and insulin-like growth factor I, along with muscle strength and muscle protein metabolism, were measured at baseline and at 1 and 6 mo of treatment. Hematological parameters were followed monthly throughout the study. Older men receiving testosterone increased total and leg LBM, muscle volume, and leg and arm muscle strength after 6 mo. LBM accretion resulted from an increase in muscle protein net balance, due to a decrease in muscle protein breakdown. TE treatment increased expression of AR protein at 1 mo, but expression returned to pre-TE treatment levels by 6 mo. IGF-I protein expression increased at 1 mo and remained increased throughout TE administration. We conclude that physiological and near-physiological increases of testosterone in older men will increase muscle protein anabolism and muscle strength. aging; muscle strength; lean body mass; insulin-like growth factor I MOST AGING MEN SHOW A REDUCTION in circulating serum testosterone concentrations (16,22). This reduction in serum testosterone concentration is a core physiological event in what is termed andropause. Andropause can be clinically characterized by decreased potency and libido, increased fatigability, and decreased muscle strength (13,24). A significant decrease in serum total testosterone occurs as early as ages 50-59 (16). This decrease in testosterone production is associated with the loss of lean body mass (LBM) and muscle strength. When men are made hypogonadal with a gonadotropin-releasing hormone analog (14), LBM and muscle strength are lost. Once weakened, older individuals are prone to falls that prevent an independent living status and diminish the quality of life. As the population of older Americans grows, the need to develop therapies to counteract the aging-induced loss in skeletal muscle mass and function becomes critically important.Previously we demonstrated that testosterone administration primes skeletal muscle for growth by increasing net protein synthesis in the fasted state (10, 18). The logic...

Aging men develop a significant loss of muscle strength that occurs in conjunction with a decline in serum testosterone concentrations. We investigated the effects of testosterone administration to six healthy men [67 +/- 2 (SE) yr] on skeletal muscle protein synthesis, strength, and the intramuscular insulin-like growth factor I (IGF-I) system. Elderly men with serum testosterone concentrations of 480 ng/dl or less were given testosterone injections for 4 wk to produce serum concentrations equal to those of younger men. During testosterone administration muscle strength (isokinetic dynamometer) increased in both right and left hamstring and quadricep muscles as did the fractional synthetic rate of muscle protein (stable-isotope infusion). Ribonuclease protection assays done on total RNA from muscle showed that testosterone administration increased mRNA concentrations of IGF-I and decreased mRNA concentrations of insulin-like growth factor binding protein-4. We conclude that increasing testosterone concentrations in elderly men increases skeletal muscle protein synthesis and strength. This increase may be mediated by stimulation of the intramuscular IGF-I system.

EAA improved LBM and basal muscle protein synthesis in older individuals. The acute anabolic response to EAA supplementation is maintained over time and can improve LBM, possibly offsetting the debilitating effects of sarcopenia.

Traumatic brain injury (TBI) is a major public health issue, and yet medical science has little to offer for the persistent symptoms that prevent many of these individuals from fully re-entering society. Post-traumatic hypopituitarism, and specifically growth hormone deficiency (GHD), has been found in a large percentage of individuals with chronic moderate to severe TBI. Presently, there are no published treatment studies of hormone replacement in this population. In this study, 83 subjects with chronic TBI were screened for hypopituitarism. Forty-two subjects were found to have either GHD or GH insufficiency (GHI), of which 23 agreed to be randomized to either a year of GH replacement or placebo. All subjects completed the study with no untoward side effects from treatment. A battery of neuropsychological tests and functional measures were administered before and after treatment. Improvement was seen on the following tests: Dominant Hand Finger Tapping Test, Wechsler Adult Intelligence Scale III-Information Processing Speed Index, California Verbal Learning Test II, and the Wisconsin Card Sorting Test (executive functioning). The findings of this pilot study provide preliminary evidence suggesting that some of the cognitive impairments observed in persons who are GHD/GHI after TBI may be partially reversible with appropriate GH replacement therapy.

Prevalence of the skin lesion acanthosis nigricans was determined in two tribal communities in Texas and Nebraska. Thirty-eight percent of the Alabama-Coushatta tribe of Texas had acanthosis nigricans. Nineteen percent of Omaha and Winnebago tribal children had the skin lesion; the youngest children had the least acanthosis nigricans. Among weight-matched Alabama-Coushatta, fasting insulin concentrations were twofold higher in subjects with the lesion. It was concluded that acanthosis nigricans is highly prevalent among Native Americans and that its presence suggests insulin resistance. Thus, it may identify those with the highest risk for non-insulin-dependent diabetes mellitus in this population.