The Systemic Effects of Exercise on Regulators of Muscle and Bone in Girls and Women

in Pediatric Exercise Science
Restricted access

Purchase article

USD  $24.95

Student 1 year online subscription

USD  $69.00

1 year online subscription

USD  $92.00

Student 2 year online subscription

USD  $131.00

2 year online subscription

USD  $175.00

Purpose: To assess the systemic effects of an acute bout of moderate-intensity exercise on factors that are known to regulate muscle and bone growth in prepubertal girls and women. Methods: A total of 12 prepubertal girls (8–10 y) and 12 women (20–30 y) cycled at 60% maximal oxygen uptake for 1 hour followed by 1 hour recovery. Blood samples were collected at rest, mid-exercise, end of exercise, mid-recovery, and end of recovery. Plasma was analyzed for interleukin-6, chemokine ligand 1, fibroblast growth factor-2, total insulin growth factor-1 (IGF-1), and free IGF-1 using enzyme-linked immunosorbent assays assays. Results: Both groups had similar concentrations of systemic factors at baseline with the exception of free IGF-1, which was higher in girls (P = .001). Interleukin-6 response was lower in girls versus women (P = .04), with a difference of +105.1% at end of exercise (P < .001), +113.5% at mid-recovery (P = .001), and +93.2% at end of recovery (P = .02). Girls and women exhibited significant declines in chemokine ligand 1, fibroblast growth factor-2, and total IGF-1 during recovery. Conclusion: Compared with women, an acute bout of moderate-intensity exercise in girls elicits a lower inflammatory response, suggesting that other mechanisms may be more important for driving the anabolic effects of exercise on muscle and bone in girls.

Mezil, Obeid, Raha, and Timmons are with the Child Health & Exercise Medicine Program, Department of Pediatrics, McMaster University, Hamilton, ON, Canada. Hawke is with the Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.

Timmons (timmonbw@mcmaster.ca) is corresponding author.
  • 1.

    Al-Shanti N, Stewart CE. Inhibitory effects of IL-6 on IGF-1 activity in skeletal myoblasts could be mediated by the activation of SOCS-3. J Cell Biochem. 2012;113(3):92333. PubMed ID: 22033984 doi:10.1002/jcb.23420

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Amir R, Ben-Sira D, Sagiv M. IGF-I and FGF-2 responses to wingate anaerobic test in older men. J Sports Sci Med. 2007;6(2):227237. PubMed ID: 24149333

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Arikawa AY, Kurzer MS, Thomas W, Schmitz KH. No effect of exercise on insulin-like growth factor (IGF)-1, insulin and glucose in young women participating in a 16-week randomized controlled trial. Cancer Epidemiol Biomarkers Prev. 2010;19(11):298790. doi:10.1158/1055-9965.EPI-10-0828

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Aviles RJ, Annex BH, Lederman RJ. Testing clinical therapeutic angiogenesis using basic fibroblast growth factor (FGF-2). Br J Pharmacol. 2003;140(4):63746. PubMed ID: 14534147 doi:10.1038/sj.bjp.0705493

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Bikle DD, Tahimic C, Chang W, Wang Y, Philippou A, Barton ER. Role of IGF-I signaling in muscle bone interactions. Bone. 2015;80:7988. PubMed ID: 26453498 doi:10.1016/j.bone.2015.04.036

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Bilek LD, Waltman NL, Lappe JM, et al. Protocol for a randomized controlled trial to compare bone-loading exercises with risedronate for preventing bone loss in osteopenic postmenopausal women. BMC Womens Health. 2016;16(1):59. PubMed ID: 27576310 doi:10.1186/s12905-016-0339-x

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    Boonen S, Rosen C, Bouillon R, et al. Musculoskeletal effects of the recombinant human IGF-I/IGF binding protein-3 complex in osteoporotic patients with proximal femoral fracture: a double-blind, placebo-controlled pilot study. J Clin Endocrinol Metab. 2002; 87(4):15939. PubMed ID: 11932288 doi:10.1210/jcem.87.4.8426

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Breen EC, Johnson EC, Wagner H, Tseng HM, Sung LA, Wagner PD. Angiogenic growth factor mRNA responses in muscle to a single bout of exercise. J Appl Physiol. 1996;81(1):35561. PubMed ID: 8828685 doi:10.1152/jappl.1996.81.1.355

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Brotto M, Bonewald L. Bone and muscle: interactions beyond mechanical. Bone. 2015;80:10914. PubMed ID: 26453500 doi:10.1016/j.bone.2015.02.010

  • 10.

    Bruserud Ø, Grovan F, Lindås R, Blymke Møinichen C, Østerhus KK. Serum levels of angioregulatory mediators in healthy individuals depend on age and physical activity: studies of angiogenin, basic fibroblast growth factor, leptin and endostatin. Scand J Clin Lab Invest. 2005;65(6):50512. PubMed ID: 16179284 doi:10.1080/00365510500209306

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Carson JA, Manolagas SC. Effects of sex steroids on bones and muscles: similarities, parallels, and putative interactions in health and disease. Bone. 2015;80:6778. PubMed ID: 26453497 doi:10.1016/j.bone.2015.04.015

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Catoire M, Mensink M, Kalkhoven E, Schrauwen P, Kersten S. Identification of human exercise-induced myokines using secretome analysis. Physiol Genomics. 2014;46(7):25667. PubMed ID: 24520153 doi:10.1152/physiolgenomics.00174.2013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Eliakim A, Nemet D, Most G, Rakover N, Pantanowitz M, Meckel Y. Effect of gender on the GH-IGF-I response to anaerobic exercise in young adults. J Strength Cond Res. 2014;28(12):34115. PubMed ID: 24983853 doi:10.1519/JSC.0000000000000605

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Eliakim A, Scheett TP, Newcomb R, Mohan S, Cooper DM. Fitness, training, and the growth hormone→insulin-like growth factor i axis in prepubertal girls. J Clin Endocrinol Metab. 2001;86(6):2797802. PubMed ID: 11397890

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Esnafoglu E, Ayyıldız SN. Decreased levels of serum fibroblast growth factor-2 in children with autism spectrum disorder. Psychiatry Res. 2017;257:7983. PubMed ID: 28734240 doi:10.1016/j.psychres.2017.07.028

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Forbes SC, Little JP, Candow DG. Exercise and nutritional interventions for improving aging muscle health. Endocrine. 2012;42(1):2938. PubMed ID: 22527891 doi:10.1007/s12020-012-9676-1

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Gu J-W, Gadonski G, Wang J, Makey I, Adair TH. Exercise increases endostatin in circulation of healthy volunteers. BMC Physiol. 2004;4(1):2. doi:10.1186/1472-6793-4-2

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Gu JW, Santiago D, Olowe Y, Weinberger J. Basic fibroblast growth factor as a biochemical marker of exercise-induced ischemia. Circulation. 1997;95(5):11658. PubMed ID: 9054845 doi:10.1161/01.CIR.95.5.1165

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Hamrick MW. A Role for Myokines in Muscle-Bone Interactions. Exerc Sport Sci Rev. 2011;39(1):437. PubMed ID: 21088601 doi:10.1097/JES.0b013e318201f601

  • 20.

    Hamrick MW. The skeletal muscle secretome: an emerging player in muscle-bone crosstalk. Bonekey Rep. 2012;1:60. PubMed ID: 23951457 doi:10.1038/bonekey.2012.60

  • 21.

    Hanssen KE, Kvamme NH, Nilsen TS, et al. The effect of strength training volume on satellite cells, myogenic regulatory factors, and growth factors. Scand J Med Sci Sports. 2013;23(6):72839. PubMed ID: 22417199 doi:10.1111/j.1600-0838.2012.01452.x

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22.

    Juul A, Holm K, Kastrup KW, et al. Free insulin-like growth factor I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab. 1997;82(8):2497502. PubMed ID: 925332

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    Kim J-S, Yoon DH, Kim H, Choi M, Song W. Resistance exercise reduced the expression of fibroblast growth factor-2 in skeletal muscle of aged mice. Integr Med Res. 2016;5(3):2305. PubMed ID: 28462123 doi:10.1016/j.imr.2016.05.001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Koizumi K, Saitoh Y, Minami T, et al. Role of CX3CL1/fractalkine in osteoclast differentiation and bone resorption. J Immunol. 2009;183(12):782531.

  • 25.

    Medeiros RMV, Arrais RF, de Azevedo JCV, et al. [Contribution of anthropometric characteristics to pubertal stage prediction in young male individuals]. Rev Paul Pediatr. 2014;32(3):22935. PubMed ID: 25479854 doi:10.1590/0103-0582201432313

    • Search Google Scholar
    • Export Citation
  • 26.

    Mezil YA, Allison D, Kish K, et al. Response of bone turnover markers and cytokines to high-intensity low-impact exercise. Med Sci Sports Exerc. 2015;47(7):1495502. PubMed ID: 25373482 doi:10.1249/MSS.0000000000000555

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27.

    Cianferotti L, Brandi ML. Muscle-bone interactions: basic and clinical aspects. Endocrine. 45(2):16577.

  • 28.

    Naganawa T, Xiao L, Abogunde E, et al. In vivo and in vitro comparison of the effects of FGF-2 null and haplo-insufficiency on bone formation in mice. Biochem Biophys Res Commun. 2006;339(2):4908. PubMed ID: 16298332 doi:10.1016/j.bbrc.2005.10.215

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Nemet D, Hong S, Mills PJ, Ziegler MG, Hill M, Cooper DM. Systemic vs local cytokine and leukocyte responses to unilateral wrist flexion exercise. J Appl Physiol. 2002;93(2):54654.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30.

    Nemet D, Mills PJ, Cooper DM. Effect of intense wrestling exercise on leucocytes and adhesion molecules in adolescent boys. Br J Sports Med. 2004;38(2):1548. PubMed ID: 15039250 doi:10.1136/bjsm.2002.002576

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31.

    Nemet D, Oh Y, Kim H-S, Hill M, Cooper DM. Effect of intense exercise on inflammatory cytokines and growth mediators in adolescent boys. Pediatrics. 2002;110(4):6819. PubMed ID: 12359780

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32.

    Nindl BC, Pierce JR. Insulin-like growth factor i as a biomarker of health, fitness, and training status. Med Sci Sports Exerc. 2010;42(1):3949. PubMed ID: 20010131 doi:10.1249/MSS.0b013e3181b07c4d

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 33.

    Northoff H, Symons S, Zieker D, et al. Gender- and menstrual phase dependent regulation of inflammatory gene expression in response to aerobic exercise. Exerc Immunol Rev. 2008;14:86103. PubMed ID: 19203086

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34.

    Olver TD, Reid SM, Smith AR, et al. Effects of acute and chronic interval sprint exercise performed on a manually propelled treadmill on upper limb vascular mechanics in healthy young men. Physiol Rep. 2016;4(13):e12861. PubMed ID: 27405970 doi:10.14814/phy2.12861

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 35.

    Pedersen BK, Febbraio MA. Muscles, exercise and obesity: skeletal muscle as a secretory organ. Nat Rev Endocrinol. 2012;8(8):45765. PubMed ID: 22473333 doi:10.1038/nrendo.2012.49

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36.

    Ploeger HE, Takken T, de Greef MHG, Timmons BW. The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review. Exerc Immunol Rev. 2009;15:641. PubMed ID: 19957870

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 37.

    Roubenoff R, Parise H, Payette HA, et al. Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham heart study. Am J Med. 2003;115(6):42935. PubMed ID: 14563498 doi:10.1016/j.amjmed.2003.05.001

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 38.

    Samaan MC, Obeid J, Nguyen T, Thabane L, Timmons BW. Chemokine (C-C motif) ligand 2 is a potential biomarker of inflammation & physical fitness in obese children: a cross-sectional study. BMC Pediatr. 2013;13(1):47. doi:10.1186/1471-2431-13-47

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 39.

    Samee N, Geoffroy V, Marty C, et al. Dlx5, a positive regulator of osteoblastogenesis, is essential for osteoblast-osteoclast coupling. Am J Pathol. 2008;173(3):77380. PubMed ID: 18669617 doi:10.2353/ajpath.2008.080243

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40.

    Scheett TP. The effect of endurance-type exercise training on growth mediators and inflammatory cytokines in pre-pubertal and early pubertal males. Pediatr Res. 2002;52(4):4917. PubMed ID: 12357041 doi:10.1203/00006450-200210000-00006

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41.

    Scheett TP, Mills PJ, Ziegler MG, Stoppani J, Cooper DM. Effect of exercise on cytokines and growth mediators in prepubertal children. Pediatr Res. 1999;46(4):429434. PubMed ID: 10509363 doi:10.1203/00006450-199910000-00011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42.

    Shojaei EA, Farajov A, Jafari A. Effect of moderate aerobic cycling on some systemic inflammatory markers in healthy active collegiate men. Int J Gen Med. 2011;4:7984. PubMed ID: 21403796 doi:10.2147/IJGM.S15065

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43.

    Strömberg A, Olsson K, Dijksterhuis JP, Rullman E, Schulte G, Gustafsson T. CX3CL1--a macrophage chemoattractant induced by a single bout of exercise in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2016;310(3):R297304.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 44.

    Tian F, Wang Y, Bikle DD. IGF-1 signaling mediated cell-specific skeletal mechano-transduction. J Orthop Res. 2018;36(2):57683. PubMed ID: 28980721

  • 45.

    Timmons BW. Paediatric exercise immunology: health and clinical applications. Exerc Immunol Rev. 2005;11:10844. PubMed ID: 16385848

  • 46.

    Tirakitsoontorn P, Nussbaum E, Moser C, Hill M, Cooper DM. Fitness, acute exercise, and anabolic and catabolic mediators in cystic fibrosis. Am J Respir Crit Care Med. 2001;164(8):14327. doi:10.1164/ajrccm.164.8.2102045

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 47.

    Tobias JH. At the crossroads of skeletal responses to estrogen and exercise. Trends Endocrinol Metab. 2003;14(10):4413. PubMed ID: 14643056 doi:10.1016/j.tem.2003.09.010

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 48.

    Urso ML, Fiatarone Singh MA, Ding W, Evans WJ, Cosmas AC, Manfredi TG. Exercise training effects on skeletal muscle plasticity and IGF-1 receptors in frail elders. Age. 2005;27(2):11725. PubMed ID: 23598617

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 49.

    Venken K, Movérare-Skrtic S, Kopchick JJ, et al. Impact of androgens, growth hormone, and IGF-I on bone and muscle in male mice during puberty. J Bone Miner Res. 2007;22(1):7282. PubMed ID: 17014385 doi:10.1359/jbmr.060911

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50.

    Vestergaard PF, Hansen M, Frystyk J, et al. Serum levels of bioactive IGF1 and physiological markers of ageing in healthy adults. Eur J Endocrinol. 2014;170(2):22936. PubMed ID: 24179101 doi:10.1530/EJE-13-0661

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 51.

    Vicente-Rodríguez G. How does exercise affect bone development during growth? Sports Med. 2006;36(7):5619.

  • 52.

    Wahl P, Zinner C, Achtzehn S, Behringer M, Bloch W, Mester J. Effects of acid-base balance and high or low intensity exercise on VEGF and bFGF. Eur J Appl Physiol. 2011;111(7):140513. doi:10.1007/s00421-010-1767-1

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 53.

    Yamashita A, Yonemitsu Y, Okano S, et al. Fibroblast growth factor-2 determines severity of joint disease in adjuvant-induced arthritis in rats. J Immunol. 2002;168(1):4507.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 267 267 43
Full Text Views 23 23 3
PDF Downloads 12 12 1