Expression of growth hormone (GH)/insulin-like growth factor (IGF) axis during Balb/c ontogeny and effects of GH upon ex-vivo T-cell differentiation

Aims: We here address the question of expression and role of 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. Effect of GH on T-cell differentiation was explored through 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 concentration 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 GHR
antagonist pegvisomant. However, GH treatment also induced a significant decrease in FTOC Gh,
Ghr and Igf1 expression.
Conclusion: 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.