Growth Hormone Mediates the Growth of TLymphoblast Cell Lines via Locally Generated Insulin-Like Growth Factor-I*

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Abstract
It has become evident that locally produced insulin-like growth factors-I and -II (IGF-I and IGF-II) play an important role in the mediation of GH action upon tissues. To explore this concept with respect to immunocompetent cells, we analyzed IGF production and clonogenic responsiveness of immortalized human T-cell lines established from seven normal controls and four Laron dwarfs. While the normal T-cell lines showed significant augmentation of basal colony formation in response to both IGF-I and GH, little increase in clonogenesis in response to GH was seen with the Laron T-cell lines. Assay of basal and GH-stimulated conditioned media demonstrated low, but measurable, levels of IGF-I and IGF-II from both normal and Laron T-cells. Under serum-free incubation conditions, GH stimulation of normal T-cell lines failed to generate significant increases in mean IGF-I or IGF-II concentrations. Only a marginal increase in the mean IGF-I concentration and no increase in the mean IGF-II concentration in conditioned medium were observed after GH stimulation of Laron T-cell lines. Nevertheless, the increased cloning efficiency of the normal T-cell lines in response to either GH or IGF-I was nearly completely abrogated by preincubation of cells with antibodies to either IGF-I or the type I IGF receptor. These studies, thus, support a role for locally generated IGF-I in the mediation of GH action of T-lymphocytes and indicated that this effect is mediated via the type I IGF receptor.