Growth Hormone, Growth Factors and Hematopoiesis

作者：Keith W. Kelley, Seán Arkins, Christian T. Minshall, Qiang Liu, Robert Dantzer · 发表于：Hormone Research · 年份：2008 · DOI：10.1159/000184757 · 被引用次数：80 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Cancer, Hypoxia, and Metabolism、Hematopoietic Stem Cell Transplantation

Hypocellularity of primary lymphoid organs is a distinctive and reproducible characteristic of aged humans and animals. Similar changes have been reported in both hypophysectomized and dwarf rodents. In the bone marrow of these animals, there is an associated reduction in the number of erythroid, lymphoid and myeloid elements. Implantation of growth hormone (GH)-secreting GH3 pituitary cells or infusion of growth hormone into aged rodents dramatically improves cellularity of both the thymus gland and bone marrow. At present it is unknown whether these effects are due to direct effects of growth hormone on hematopoietic cells or if they are caused by the induction of insulin-like growth factor-1 (IGF-1) synthesis. We recently discovered that colony-stimulating factor-1 (CSF-1) and interleukin-3 (IL-3) induce expression and synthesis of the IGF-1 peptide in murine bone marrow cells. Transcripts for IGF-1 increase approximately 50-fold during differentiation over the negligible levels that are expressed in freshly isolated bone marrow cells. Two potential functions of macrophage-derived IGF-1 are to: (a) increase the proliferation of early or committed bone marrow progenitors and (b) reduce their rate of cell death. In support of the first possibility, IGF binding protein-3 significantly inhibits the proliferation of CSF-1-treated bone marrow cells and this inhibition can be reversed by addition of exogenous IGF-1. In support of the second possibility, we have induced apoptosis ...