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

To investigate the potential effects of growth hormone (GH) on the hem atopoietic system, mice transgenic for bovine GH (bGH) or human growth hormone releasing hormone (hGRH) genes, each of which can result in t he constitutive overproduction of GH, were analyzed for splenic and bo ne marrow (BM) localized hematopoietic progenitor cells. These transge nic mice had splenic hyperplasia with increased absolute numbers of sp lenic 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 hig h proportion (54-71%) of splenic erythroid, granulocyte-macrophage, an d megakaryocyte progenitors were in cycle in transgenic mice in contra st to less than or equal to 30% in nontransgenic control littermates. Compared to controls, splenocytes from hGRH mice had a significantly h igher proliferative index when infused into irradiated nontransgenic c ontrols. With the exception of the megakaryocyte colony assay and in v ivo proliferative index, none of these findings were evident when iden tical assays were performed on the BM from the same mice. Consistent w ith the BM data, peripheral blood leukocyte, erythroid, and platelet n umbers were comparable in transgenic and nontransgenic control litterm ates. We conclude that the constitutive expression of bGH or hGRH lead s largely to splenic hematopoietic effects involving progenitor cell p opulations from at least two lineages.