GROWTH-HORMONE RECEPTOR AND REGULATION OF GENE-EXPRESSION IN FETAL LYMPHOID-CELLS

The role of growth hormone (GH) in modulating the adult immune respons e is receiving increased attention; however, its role in the developme nt 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 respons e, cells from bovine fetal spleen and thymus were examined for GH rece ptor and responsiveness to GH. Northern analysis and ligand binding st udies showed that growth hormone receptor (GHR) was readily detected i n early- and mid-gestational fetal thymocytes, but it was less readily detected in thymocytes from older fetuses. In contrast, GHR was easil y detected in splenocytes at all fetal ages. Thymocytes and splenocyte s from mid-gestational fetuses expressed low levels of cell surface GH R by flow cytofluorometric analysis, and CD4(+) and CD8(+)(single posi tive) thymocyte subsets were positive. Northern analyses were employed to determine the effects of in vitro GH treatment on expression of se veral proto-oncogenes, cytokines, and GHR in thymocytes from fetuses a t approximately mid-gestation. GH treatment for 30 min down-regulated c-jun and c-fos mRNA approximate to 2- and 2.8-fold, respectively. Aft er 6 h treatment, GH increased transcript levels for interleukin OL)-1 alpha, IL-1 beta, IL-6, and GM-CSF about 2.5-, 2.2-, 3-, and 2-fold, respectively. GH also down-regulated the expression of its own recepto r 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 pote ntial role for GH in the development and/or function of the fetal bovi ne immune system. Although the mechanism(s) is unclear, our results su ggest that GH is intimately involved in lymphocyte function and expres sion of certain cytokines during a critical period of fetal immune dev elopment. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.