{Reference Type}: Journal Article {Title}: Relative rDNA copy number is not associated with resistance training-induced skeletal muscle hypertrophy and does not affect myotube anabolism in vitro. {Author}: Godwin JS;Michel JM;Ludlow AT;Frugé AD;Mobley CB;Nader GA;Roberts MD; {Journal}: Am J Physiol Regul Integr Comp Physiol {Volume}: 327 {Issue}: 3 {Year}: 2024 Sep 1 {Factor}: 3.21 {DOI}: 10.1152/ajpregu.00131.2024 {Abstract}: Ribosomal DNA (rDNA) copies exist across multiple chromosomes, and interindividual variation in copy number is speculated to influence the hypertrophic response to resistance training. Thus, we examined if rDNA copy number was associated with resistance training-induced skeletal muscle hypertrophy. Participants (n = 53 male, 21 ± 1 yr old; n = 29 female, 21 ± 2 yr old) performed 10-12 wk of full-body resistance training. Hypertrophy outcomes were determined, as was relative rDNA copy number from preintervention vastus lateralis (VL) biopsies. Pre- and postintervention VL biopsy total RNA was assayed in all participants, and mRNA/rRNA markers of ribosome content and biogenesis were also assayed in the 29 female participants before training, 24 h following training bout 1, and in the basal state after 10 wk of training. Across all participants, no significant associations were evident between relative rDNA copy number and training-induced changes in whole body lean mass (r = -0.034, P = 0.764), vastus lateralis thickness (r = 0.093, P = 0.408), mean myofiber cross-sectional area (r = -0.128, P = 0.259), or changes in muscle RNA concentrations (r = 0.026, P = 0.818), and these trends were similar when examining each gender. However, all Pol-I regulon mRNAs as well as 45S pre-rRNA, 28S rRNA, and 18S rRNA increased 24 h following the first training bout in female participants. Follow-up studies using LHCN-M2 myotubes demonstrated that a reduction in relative rDNA copy number induced by bisphenol A did not significantly affect insulin-like-growth factor-induced myotube hypertrophy. These findings suggest that relative rDNA copy number is not associated with myofiber hypertrophy.NEW & NOTEWORTHY We examined ribosomal DNA (rDNA) copy numbers in men and women who resistance trained for 10-12 wk and found no significant associations with skeletal muscle hypertrophy outcomes. These data, along with in vitro data in immortalized human myotubes whereby rDNA copy number was reduced, provide strong evidence that relative rDNA copy number is not associated with anabolism.