The role of lymphocyte derived growth hormone in cells of the immune system

A body of literature has shown that both primary cells of the immune system and cell lines produce growth hormone (GH) and insulin like growth factors (IGFs) independently of the endocrine system. The range of biological activities of lymphocyte derived growth hormone remains undefined but the literature suggests that lymphocyte derived growth hormone may influence lymphocyte activation, apoptosis, and transformation. Previous work using the murine growth hormone receptor (GHR) negative EL4 lymphoma cell line overexpressing growth hormone (GHo) has shown that growth hormone may function in an intracrine manner in the absence of the GHR. This work demonstrated that GHo protects EL4 cells from chemically induced apoptosis by increasing IGF-1, IGF-1R, and iNOS expression. The current studies show that lymphocyte derived growth hormone increases expression of functional insulin like growth factor-2 receptor (IGF-2R) and transforming growth factor-beta 1 (TGF-beta1) in GHo EL4 cells compared to vector alone control cells. The data show that GHo cells express more IGF-2R and TGF-beta1 at the promoter and protein levels as measured by luciferase promoter assay and western analysis, respectively. We also show that the increase in IGF-2R is an increase in functional IGF-2R as measured by 125IGF-2 uptake. Additionally, GHo increases the conversion of latent TGF-beta1 to active TGF-beta1. GH-AS but not GH-S oligodeoxynucleotides inhibit basal TGF-beta1 expression in EL4 cells not overexpressing GH. Finally we show alpha-TGF-betaR2 but not alpha-GH antibody can block TGF-beta1 expression in EL4 GHo cells which suggests that the increase in TGF-beta1 expression in GHo cells may be mediated through TGF-betaR2 which is consistent with autoinduction of TGF-beta1 expression. Taken together the data suggest that lymphocyte derived growth hormone exerts complex intracrine effects in lymphocytes by modulating IGF-R and TGF-beta1 expression and activation.