Growth Hormone, Growth Factors and Hematopoiesis

Abstract

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 of both nonadherent bone marrow cells and a myeloid progenitor cell line by depriving these cells of CSFs. Preliminary results indicate that addition of IGF-1 to these cells reduces apoptotic cell death by 50%. These data establish that two different CSFs, CSF-1 and IL-3, induce abundant expression of IGF-1 as these cells differentiate into more mature hematopoietic cells. This model offers a novel approach for investigating the developmental expression of IGF-1 during defined differentiation pathways of hematopoietic cells. If IGF-1 is indeed proven to act as a survival factor for hematopoietic progenitors, these data would support the idea that the hypocellularity of primary lymphoid tissues in aged animals is related to the limited availability to these cells of either growth hormone or IGF-1.

Colony-Stimulating Factor-1 Promotes Kidney Growth and Repair via Alteration of Macrophage Responses

“…55 Our previous report showing that CSF-1 can promote nephrogenesis in kidney explants 3 is analogous to the growth-promoting role of IGF-1 in human fetal kidney explants that supports the induction and differentiation of the nephrogenic zone. 56 The production of IGF-1 by CSF-1-stimulated macrophages has been recognized previously, 52,57,58 but no comparative abundance data have previously been presented.…”

The Gfi-1B Proto-Oncoprotein Represses p21WAF1 and Inhibits Myeloid Cell Differentiation

“…The molecular mechanisms involved in regulating hematopoietic cell commitment and differentiation can be addressed in differentiating hematopoietic tissues in intact animals (64) and in cell lines that can be induced to differentiate (35,38). With both systems, a number of molecules, including growth factors, receptors, and transcription factors, have been identified and shown to contribute to hematopoiesis in a hierarchical order (10,29,42,65).…”

Growth hormone enhances thymic function in HIV-1–infected adults

“…Administration of GH or IGF-1 reverses thymic involution and enhances thymopoiesis in aged rodents (25)(26)(27) and accelerates immune reconstitution in immunodeficient animals (28,29). Previously, we hypothesized that therapies to enhance human thymopoiesis might facilitate immune restoration in HIV-1 disease.…”