Eccentric exercise activates novel transcriptional regulation of hypertrophic signaling pathways not affected by hormone changes

PLoS One. 2010 May 18;5(5):e10695. doi: 10.1371/journal.pone.0010695.


Unaccustomed eccentric exercise damages skeletal muscle tissue, activating mechanisms of recovery and remodeling that may be influenced by the female sex hormone 17beta-estradiol (E2). Using high density oligonucleotide based microarrays, we screened for differences in mRNA expression caused by E2 and eccentric exercise. After random assignment to 8 days of either placebo (CON) or E2 (EXP), eighteen men performed 150 single-leg eccentric contractions. Muscle biopsies were collected at baseline (BL), following supplementation (PS), +3 hours (3H) and +48 hours (48H) after exercise. Serum E2 concentrations increased significantly with supplementation (P<0.001) but did not affect microarray results. Exercise led to early transcriptional changes in striated muscle activator of Rho signaling (STARS), Rho family GTPase 3 (RND3), mitogen activated protein kinase (MAPK) regulation and the downstream transcription factor FOS. Targeted RT-PCR analysis identified concurrent induction of negative regulators of calcineurin signaling RCAN (P<0.001) and HMOX1 (P = 0.009). Protein contents were elevated for RND3 at 3H (P = 0.02) and FOS at 48H (P<0.05). These findings indicate that early RhoA and NFAT signaling and regulation are altered following exercise for muscle remodeling and repair, but are not affected by E2.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Blotting, Western
  • Dietary Supplements
  • Estradiol / blood*
  • Exercise / physiology*
  • Gene Expression Regulation*
  • Humans
  • Hypertrophy
  • L-Lactate Dehydrogenase / blood
  • Male
  • Muscles / pathology
  • NFATC Transcription Factors / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphorylation
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Testosterone / blood*
  • Transcription, Genetic*
  • Young Adult
  • rhoA GTP-Binding Protein / metabolism


  • Actins
  • NFATC Transcription Factors
  • RNA, Messenger
  • Testosterone
  • Estradiol
  • L-Lactate Dehydrogenase
  • rhoA GTP-Binding Protein