THE EXPRESSION OF ANDROGEN-REGULATED GENES BEFORE AND AFTER A RESISTANCE EXERCISE BOUT IN YOUNGER AND OLDER MEN MICHAEL D. ROBERTS,VINCENT J. DALBO,SCOTT E. HASSELL, AND CHAD M. KERKSICK Applied Biochemistry and Molecular Physiology Laboratory, Health and Exercise Science Department, University of Oklahoma, Norman, Oklahoma ABSTRACT Roberts, MD, Dalbo, VJ, Hassell, SE, and Kerksick, CM. The expression of androgen-regulated genes before and after a resistance exercise bout in younger and older men. J Strength Cond Res 23(4): 1060–1067, 2009—This cross-sectional study examined aging and resistance exercise–related changes in intramuscular gene expression in younger (21.3 6 0.6 years, 84.8 6 6.0 kg, 26.6 6 2.1 kgÁm 22 ; n = 11) and older men (67.6 6 1.3 years, 88.7 6 4.8 kg, 28.6 6 1.4 kgÁm 22 ; n = 13) surrounding a single bout of resistance exercise. Participants completed 3 3 10 repetitions at 80% of their 1 repetition maximum for Smith squat, leg press, and leg extension. Muscle biopsies were obtained before and 24 hours after exercise, whereas venous blood was collected before, immediately after and 24 hours after exercise. Free testosterone levels were greater in younger participants at all time points (p , 0.05), in addition to a greater increase in the younger men immediately post exercise (p , 0.01). Preexercise human growth hormone levels between age groups were similar (p . 0.05). Human growth hormone increased immediately post exercise in both groups (p , 0.05) with a greater response occurring in the younger (p , 0.001) men. Older men expressed greater levels of androgen receptor (AR) at rest (p = 0.02). A significant correlation existed between preexercise free testosterone levels basal AR gene expression (r = 20.59, p , 0.01). These data suggest that AR expression patterns may be related to circulating free testosterone levels. Although these findings do not fully unveil the genomic effects of androgen signaling and its relationship to muscle wasting conditions, these results provide a platform for future researchers seeking to employ gene therapy to remedy muscle loss. KEY WORDS aging, gene expression, muscle, hypertrophy INTRODUCTION A ging in men is associated with decrements in circulating anabolic hormones including free testosterone, total testosterone, and insulin-like growth factor-I (IGF-I) (19). Additionally, re- sistance training involving large muscle groups transiently increases the postexercise concentrations of free testosterone, total testosterone, and human growth hormone (hGH), but this response is blunted in older men (19). These hormonal decrements are hypothesized to lower resistance training– induced increases in strength and muscle mass (19). Furthermore, research has demonstrated that a decrement in circulating bioactive testosterone (i.e., free testosterone and non–sex hormone-binding globulin-bound testosterone) significantly contributes to muscle loss in aging men (29,32,14). In this regard, Baumgartner et al. (4) demon- strated that free testosterone was the most significant predictor of muscle mass in 121 men older than 65 years. From a mechanistic perspective, free testosterone operates by diffusing into skeletal muscle and binding androgen receptors (ARs) present within the cytosol and myonuclei of mature muscle fibers and satellite cells (31). Ligand-bound ARs then homodimerize and bind to androgen response elements (AREs) present on the genome to affect the rates of transcription of various genes (9). Bhasin et al. (5,30) have performed a series of clinical trials demonstrating that administering superphysiological doses of testosterone to younger and older men significantly increases lean body mass and lower-body strength, as well as serum-free testosterone, satellite cell number, and muscle fiber cross-sectional area. An additional review by these authors (16) states that testosterone likely acts to induce mesenchymal pluripotent cells to commit to the myogenic lineage, inhibit the differentiation of mesenchymal pluripotent cells into the adipogenic lineage, stimulate satellite cell replication, stim- ulate muscle protein synthesis, and reduce muscle protein degradation. Nonetheless, although the phenotypic effects of testosterone have been well documented, a limited amount of data exist depicting the genomic effects of testosterone, with current published studies in the area examining diseased humans (25) or rodents (35). Address correspondence to Chad M. Kerksick, chad_kerksick@ou.edu. 23(4)/1060–1067 Journal of Strength and Conditioning Research Ó 2009 National Strength and Conditioning Association 1060 Journal of Strength and Conditioning Research the TM