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

<i>Aims:</i> We address the question of the expression and the role of the growth hormone/insulin-like growth factor (GH/IGF) axis in the thymus. <i>Methods:</i> 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. <i>Results:</i> Transcription of <i>Gh</i>, <i>Igf1</i>, <i>Igf2</i> and their related receptors predominantly occurred in thymic epithelial cells (TEC), while a low level of <i>Gh</i> and <i>Igf1r </i>transcription was also evidenced in thymic T cells (thymocytes). <i>Gh</i>, <i>Ghr</i>, <i>Ins2</i>, <i>Igf1</i>, <i>Igf2</i>, and <i>Igfr1</i> 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 <i>Gh</i>, <i>Ghr</i> and <i>Igf1</i> expression. <i>Conclusion:</i> 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.