title: Circulating transforming growth factor beta1 (TGFbeta1) is elevated by extensive exercise.
abstract: Transforming growth factor beta1 (TGFbeta1) is a multifunctional growth factor involved in immune function, atherosclerosis, fibrotic disease, diabetic complications and bone turnover. It is synthesized in large quantities by bone cells in response to hormones and mechanical stimuli. Plasma contains inactive "latent" TGFbeta1, which consists of the precursor molecule and a TGFbeta1-binding protein. Platelets store latent TGFbeta1 in their alpha-granules, and serum therefore contains large amounts of latent TGFbeta1. We developed a technique for determining latent plasma TGFbeta1 and investigated whether circulating TGFbeta1 is affected by the stimulation of bone formation in response to strength training. Ten healthy students with low training activity participated in a heavy exercise programme over 4 weeks. Blood was drawn into citrate-filled syringes containing prostaglandin E(1) (PGE(1)) and immediately centrifuged at 4 degrees C. TGFbeta1 was determined with a sandwich ELISA standardized with National Institute for Biological Standards and Controls (NIBSC) materials. Six of the ten students completed the training. Highly reproducible values (500-600 pg/ml) of latent TGFbeta1 in plasma were determined. Baseline levels of TGFbeta1 were 525 (50) pg/ml [mean (SE)], which is in the range observed for young adults. TGFbeta1 concentrations rose significantly to 710 (65) pg/ml after 2 weeks of training and thereafter slowly declined to 650 (62) pg/ml after 2 weeks and 440 (33) pg/ml after 4 weeks, respectively. No active TGFbeta1 was detectable in citrate PGE1 plasma samples. Serum levels were between 6000 and 10,000 pg/ml and contained 200-400 pg/ml active TGFbeta1. In contrast to previous reports, plasma did not contain measurable amounts of circulating active TGFbeta1. We demonstrate that heavy exercise transiently elevates latent TGFbeta1 concentrations in plasma. TGFbeta1 is produced by osteoblasts in considerable amounts; therefore, we assume that the observed changes are partly due to enhanced TGFbeta1 production or release in bone, since the quantities of TGFbeta1 produced by other cells are comparably small.
authors.affiliation: Department of Internal Medicine, University-Hospital, BG-Clinic "Bergmannsheil", Ruhr-University Bochum, 44789 Bochum, Germany. steffen.hering@ruhr-uni-bochum.de
authors.forename: S
authors.initials: S
authors.lastname: Hering
authors.forename: C
authors.initials: C
authors.lastname: Jost
authors.forename: H
authors.initials: H
authors.lastname: Schulz
authors.forename: B
authors.initials: B
authors.lastname: Hellmich
authors.forename: H
authors.initials: H
authors.lastname: Schatz
authors.forename: H
authors.initials: H
authors.lastname: Pfeiffer
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000201:enzymology / Q000502:physiology; D003402:Creatine Kinase / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000295:instrumentation / Q000379:methods; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010807:Physical Endurance; D012016:Reference Values; D015203:Reproducibility of Results; D016212:Transforming Growth Factor beta / Q000097:blood*; D053773:Transforming Growth Factor beta1; D014508:Urea / Q000097:blood; D016474:Weight-Bearing / Q000502:physiology
chemical_list: C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D014508:Urea; D003402:Creatine Kinase; D000469:Alkaline Phosphatase