Growth Hormone–Induced Stimulation of Multilineage Human Hematopoiesis

Abstract

Growth hormone (GH) has been shown to have significant positive effects on hemato-lymphopoiesis in rodent models and, more recently, to increase thymic mass and circulating naïve CD4 + T cells in humans infected with the human immunodeficiency virus, type 1. To determine whether the latter effects on human T lymphopoiesis might be due, at least in part, to effects on the bone marrow (BM), we examined the specific effects of GH and its proximal mediator, insulin-like growth factor I (IGF-I), on human multilineage hematopoiesis in fetal BM (FBM). Using in vitro analysis, we found that GH and IGF-I each stimulated the expansion of primitive multilineage CD34 + CD38 − hematopoietic progenitor cells and increased yields of several hematopoietic subpopulations, including CD34 + CD38 + CD10 + lymphoid progenitor cells. Additionally, GH and IGF-I had direct effects on FBM stromal elements,inducing the expansion of myeloid-like CD45

Recombinant human GH replacement increases CD34+ cells and improves endothelial function in adults with GH deficiency

“…In addition, CD34C cells express both GH and IGF-I receptors (33) as is the case for several other cell types that could be involved. Indeed, studies in rodents and on fetal bone marrow demonstrate direct effects of GH and IGF-I on hematopoiesis (33,34). It is likely that complex interactions between circulating IGF-I, IGFBP-3, and their effects on nitric-oxide bioavailability result in the increase in CD34C cells in our study.…”

“…Indeed, GH treatment was found to induce markers of nitric oxide bioavailability in healthy volunteers (27). In addition, CD34C cells express both GH and IGF-I receptors (33) as is the case for several other cell types that could be involved. Indeed, studies in rodents and on fetal bone marrow demonstrate direct effects of GH and IGF-I on hematopoiesis (33,34).…”

TLR agonists induce the differentiation of human bone marrow CD34+ progenitors into CD11c+ CD80/86+ DC capable of inducing a Th1‐type response

“…Cells were also stained with antibody-matched IgG isotype controls. The data are representative of five independent experiments, which are summarized in [21][22][23]. Among the cytokines produced by CD34 + after TLR ligation are TNF-a and GM-CSF (Fig.…”

Growth hormone receptor signaling is dispensable for HSC function and aging

“…2 Growth hormone (Gh) signaling has been implicated in a variety of age-related hematopoietic phenotypes, [3][4][5] and exogenous Gh can enhance or restore young or aged hematopoietic cellularity and function, respectively. [5][6][7][8][9][10] Studies have proposed that Gh mediates its hematopoietic effects indirectly through nonhematopoietic cells within the bone marrow (BM) 7,11 ; however, as the Gh responsive cell was not identified in these studies, it remains unclear whether Gh directly targets hematopoietic stem/progenitor cells in a cell autonomous manner. Here, we have addressed the cell intrinsic impact of Gh signaling on HSCs during aging using gain-of-function and loss-of-function approaches.…”