Growth hormone receptor and regulation of gene expression in fetal lymphoid cells

Abstract

The role of growth hormone (GH) in modulating the adult immune response is receiving increased attention; however, its role in the development of immune competence in the fetus has not been defined. In order to begin to address the role of GH in the ontogeny of the immune response, cells from bovine fetal spleen and thymus were examined for GH receptor and responsiveness to GH. Northern analysis and ligand binding studies showed that growth hormone receptor (GHR) was readily detected in early- and mid-gestational fetal thymocytes, but it was less readily detected in thymocytes from older fetuses. In contrast, GHR was easily detected in splenocytes at all fetal ages. Thymocytes and splenocytes from mid-gestational fetuses expressed low levels of cell surface GHR by flow cytofluorometric analysis, and CD4 +and CD8 +(single positive) thymocyte subsets were positive. Northern analyses were employed to determine the effects of in vitro GH treatment on expression of several proto-oncogenes, cytokines, and GHR in thymocytes from fetuses at approximately mid-gestation. GH treatment for 30 min down-regulated c-jun and c-fos mRNA ≈2- and 2.8-fold, respectively. After 6 h treatment, GH increased transcript levels for interleukin (IL)-1 α, IL-1 β, IL-6, and GM-CSF about 2.5-, 2.2-, 3-, and 2-fold, respectively. GH also down-regulated the expression of its own receptor about 3.2-fold after 8 h of incubation. The presence of GHR in fetal lymphoid cells and its temporal and spatial regulation suggest a potential role for GH in the development and/or function of the fetal bovine immune system. Although the mechanism(s) is unclear, our results suggest that GH is intimately involved in lymphocyte function and expression of certain cytokines during a critical period of fetal immune development.