title: Eccentric exercise activates novel transcriptional regulation of hypertrophic signaling pathways not affected by hormone changes.
abstract: 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.
authors.affiliation: Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Lauren G
authors.initials: LG
authors.lastname: MacNeil
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Alan E
authors.initials: AE
authors.lastname: Hubbard
authors.forename: Steven K
authors.initials: SK
authors.lastname: Baker
authors.forename: Mark A
authors.initials: MA
authors.lastname: Tarnopolsky
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D019587:Dietary Supplements; D004958:Estradiol / Q000097:blood*; D015444:Exercise / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D006984:Hypertrophy; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009132:Muscles / Q000473:pathology; D050778:NFATC Transcription Factors / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D013739:Testosterone / Q000097:blood*; D014158:Transcription, Genetic; D055815:Young Adult; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D050778:NFATC Transcription Factors; D012333:RNA, Messenger; D013739:Testosterone; D004958:Estradiol; D007770:L-Lactate Dehydrogenase; D020742:rhoA GTP-Binding Protein