title: Increased serum and bone matrix levels of transforming growth factor {beta}1 in patients with GH deficiency in response to GH treatment.
abstract: OBJECTIVE
  Patients with adult onset GH deficiency (aoGHD) have secondary osteoporosis, which is reversed by long-term GH substitution. Transforming growth factor β1 (TGFβ1 or TGFB1) is abundant in bone tissue and could mediate some effects of GH/IGFs on bone. We investigated its regulation by GH/IGF1 in vivo and in vitro.
  
  
  METHODS
  The effects of GH substitution (9-12 months, placebo controlled) on circulating and cortical bone matrix contents of TGFβ1 were investigated in patients with aoGHD. The effects of GH/IGF1 on TGFβ1 secretion in osteoblasts (hFOB), adipocytes, and THP-1 macrophages as well as the effects on release from platelets were investigated in vitro.
  
  
  RESULTS
  In vivo GH substitution increased TGFβ1 protein levels in cortical bone and serum. In vitro, GH/IGF1 stimulation induced a significant increase in TGFβ1 secretion in hFOB. In contrast, no major effect of GH/IGF1 on TGFβ1 was found in adipocytes and THP-1 macrophages. Finally, a minor modifying effect on SFLLRN-stimulated platelet release of TGFβ1 was observed in the presence of IGF1.
  
  
  CONCLUSIONS
  GH substitution increases TGFβ1 in vivo and in vitro, and this effect could contribute to improved bone metabolism during such therapy, potentially reflecting direct effect of GH/IGF1 on bone cells.
authors.affiliation: Research Institute for Internal Medicine Department of Endocrinology Section of Clinical Immunology and Infectious Faculty of Medicine, Oslo University Hospital Rikshospitalet, University of Oslo, Oslo, Norway. thor.ueland@medisin.uio.no
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Tove
authors.initials: T
authors.lastname: Lekva
authors.forename: Kari
authors.initials: K
authors.lastname: Otterdal
authors.forename: Tuva B
authors.initials: TB
authors.lastname: Dahl
authors.forename: Nicoleta Cristina
authors.initials: NC
authors.lastname: Olarescu
authors.forename: Anders P
authors.initials: AP
authors.lastname: Jørgensen
authors.forename: Kristian J
authors.initials: KJ
authors.lastname: Fougner
authors.forename: Kim
authors.initials: K
authors.lastname: Brixen
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.forename: J
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D017667:Adipocytes / Q000378:metabolism; D000328:Adult; D001857:Bone Matrix / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000627:therapeutic use*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I