Transgenic mice expressing either bovine growth hormone (bGH) or human GH releasing hormone (hGRH) have increased splenic progenitor cell colony formation and DNA synthesis in vitro and in vivo

Abstract

To investigate the potential effects of growth hormone (GH) on the hematopoietic system, mice transgenic for bovine GH (bGH) or human growth hormone releasing hormone (hGRH) genes, each of which can result in the constitutive overproduction of GH, were analyzed for splenic and bone marrow (BM) localized hematopoietic progenitor cells. These transgenic mice had splenic hyperplasia with increased absolute numbers of splenic erythroid and megakaryocytic progenitor cells as assessed by in vitro assay and megakaryocyte development as seen in spleens. As an in vivo indication of multilineage progenitor cell effects in hGRH mice, the number of day-10 CFU-S colonies derived from the donor spleen was significantly higher than in nontransgenic littermate controls. A high proportion (54-71%) of splenic erythroid, granulocyte-macrophage, and megakaryocyte progenitors were in cycle in transgenic mice in contrast to < or = 30% in nontransgenic control littermates. Compared to controls, splenocytes from hGRH mice had a significantly higher proliferative index when infused into irradiated nontransgenic controls. With the exception of the megakaryocyte colony assay and in vivo proliferative index, none of these findings were evident when identical assays were performed on the BM from the same mice. Consistent with the BM data, peripheral blood leukocyte, erythroid, and platelet numbers were comparable in transgenic and nontransgenic control littermates. We conclude that the constitutive expression of bGH or hGRH leads largely to splenic hematopoietic effects involving progenitor cell populations from at least two lineages.