title: Expression of the growth hormone/insulin-like growth factor axis during Balb/c thymus ontogeny and effects of growth hormone upon ex vivo T cell differentiation.
abstract: OBJECTIVE
  We address the question of the expression and the role of the growth hormone/insulin-like growth factor (GH/IGF) axis in the thymus.
  
  
  METHODS
  Using RT-qPCR, the expression profile of various components of the somatotrope GH/IGF axis was measured in different thymic cell types and during thymus embryogenesis in Balb/c mice. The effect of GH on T cell differentiation was explored via thymic organotypic culture.
  
  
  RESULTS
  Transcription of Gh, Igf1, Igf2 and their related receptors predominantly occurred in thymic epithelial cells (TEC), while a low level of Gh and Igf1r transcription was also evidenced in thymic T cells (thymocytes). Gh, Ghr, Ins2, Igf1, Igf2, and Igfr1 displayed distinct expression profiles depending on the developmental stage. The protein concentrations of IGF-1 and IGF-2 were in accordance with the profile of their gene expression. In fetal thymus organ cultures (FTOC) derived from Balb/c mice, treatment with exogenous GH resulted in a significant increase of double negative CD4-CD8- T cells and CD4+ T cells, together with a decrease in double positive CD4+CD8+ T cells. These changes were inhibited by concomitant treatment with GH and the GH receptor (GHR) antagonist pegvisomant. However, GH treatment also induced a significant decrease in FTOC Gh, Ghr and Igf1 expression.
  
  
  CONCLUSIONS
  These data show that the thymotropic properties of the somatotrope GH/IGF-1 axis involve an interaction between exogenous GH and GHR expressed by TEC. Since thymic IGF-1 is not increased by GH treatment, the effects of GH upon T cell differentiation could implicate a different local growth factor or cytokine.
authors.affiliation: Center of Immunology, Institute of Pathology, University of Liège, CHU-B23, Liège-Sart Tilman, Belgium.
authors.forename: Hamid
authors.initials: H
authors.lastname: Kermani
authors.forename: Lindsay
authors.initials: L
authors.lastname: Goffinet
authors.forename: Marie
authors.initials: M
authors.lastname: Mottet
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Bodart
authors.forename: Gabriel
authors.initials: G
authors.lastname: Morrhaye
authors.forename: Olivier
authors.initials: O
authors.lastname: Dardenne
authors.forename: Chantal
authors.initials: C
authors.lastname: Renard
authors.forename: Lut
authors.initials: L
authors.lastname: Overbergh
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baron
authors.forename: Yves
authors.initials: Y
authors.lastname: Beguin
authors.forename: Vincent
authors.initials: V
authors.lastname: Geenen
authors.forename: Henri J
authors.initials: HJ
authors.lastname: Martens
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D013006:Growth Hormone / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009924:Organ Culture Techniques; D060888:Real-Time Polymerase Chain Reaction; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011986:Receptors, Somatotropin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D060168:Thymocytes / Q000378:metabolism; D013950:Thymus Gland / Q000196:embryology / Q000276:immunology* / Q000378:metabolism
chemical_list: C513121:IGF2 protein, mouse; C561967:Ins2 protein, mouse; D007328:Insulin; D011986:Receptors, Somatotropin; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D013006:Growth Hormone; D017526:Receptor, IGF Type 1