Studies On The Regulation Of Growth Hormone Gene Transcription In B Lymphocytes

Growth hormone (GH) has important stimulating effect on immune function and its association with immune function aroused great investigating interests. GH and its receptor could be expressed by human and rodent lymphocytes. Lymphocytic GH could affect the function of lymphocyte in an autocrine and/or paracrine way. Now the control mechanism of GH gene expression in lymphocyte is unclear. It was found that some hormones could affect lymphocyte GH secretion. Cytokines have significant impact on lymphocytic growth, differentiation and functions. There are few reports about the effects of hormones and cytokines on lymphocyte GH gene transcription. We addressed this question with the method of luciferase reporter gene. In addition, we explored the association of GH gene transcription and intracellular signaling transduction pathway, the relative transcription activity of various deletions of GH gene promoter, and the association of GH gene transcription with pituitary specific transcription factor Pit-1, in B-lymphocytes.1. The effects of cytokines and hormones on GH gene transcription in B-lymphocyte. We insert GH gene promoter (-484~+2 bp) into luciferase reporter gene vector pGL3-Enhancer. The recombinant plasmid was abbreviated as 484-luc. Then 484-luc was transfected into B-lymphocyte. Fifty-six hours after transfection, B-lymphocytes were treated with various hormones and cytokines at different concentration. Four hours later, cells were harvested and lysed to measure luciferase activity. The results demonstrated that GHRH (0.001 nM) and IL-1β (10~1000U/ml) significantly inhibited, whereas IGF-1 (1-100 nM), IL-2 (10-1000 U/ml), IL-4 (10 ng/ml), TNF-α (100-1000 U/ml) and IFN-γ (10-1000 U/ml) significantly stimulated GH transcription in B-lymphocytes. Among all the observed hormones and cytokines, IFN-γ had most prominent effect. It increased GH gene transcription in B-lymphocytes in a dose-dependent manner. When it's concentration was 1000 U/ml, GH gene transcription increased by 51 % as compared with control. SMS (a somatostatin analogue), IL-5, and IL-6 had no significant effect on GH gene transcription in B-lymphocyte. Above results suggested that the...