Human growth hormone stimulates proliferation of human retinal microvascular endothelial cells in vitro.

Abstract

Growth hormone (GH) has been implicated in the pathogenesis of proliferative diabetic retinopathy. We sought to determine whether this could be mediated by an effect of GH on proliferation of endothelial cells, and, for this purpose, established long-term cultures of human retinal microvascular endothelial cells (hREC) from normal postmortem human eyes. High-purity (>95%) hREC preparations were selected for experiments, based on immunofluorescence with acetylated low density lipoprotein (LDL) and anti-factor VIIIrelated antigen. Growth requirements for these cells were complex, including serum for maintenance at slow growth rates and additional mitogens for more rapid proliferation. Exposure ofhREC to physiologic doses ofhuman GH (hGH) resulted in 100% greater cell number vs. control (P < 0.01) but could be elicited only in the presence of serum. When differing serum conditions were compared, hGH stimulated [3H]thymidine incorporation up to 1.6-to 2.2-fold under each condition and increased DNA content significantly in the presence of human, horse, and fetal calf serum. Depending on the culture conditions used, the threshold hGH concentration for significant stimulation of hREC proliferation was 0.4-4 pg/liter. In contrast, proliferation of human umbilical vein endothelial cells was not significantly altered by hGH added to concentrations as high as 200 pzg/liter. In summary, hREC respond to physiologic concentrations of hGH in vitro with enhanced proliferation. This specific effect of GH on retinal microvascular endothelial cells supports the hypothesis of a role for GH in endothelial cell biology.

Growth Hormone Promotes Lymphangiogenesis

“…173, No. 2 of human retinal microvascular endothelial cells 32 and of bovine brain capillary endothelial cells 33 but not of human umbilical cord vein endothelial cells. 32 However, its comparative effects on LECs have not been previously characterized.…”

“…2 of human retinal microvascular endothelial cells 32 and of bovine brain capillary endothelial cells 33 but not of human umbilical cord vein endothelial cells. 32 However, its comparative effects on LECs have not been previously characterized. Importantly, GH did not only stimulate LEC proliferation, but also promoted a number of other cellular functions involved in lymphangiogenesis, including tube formation and chemotactic migration.…”

“…30 GH signaling has been implicated in promoting postnatal longitudinal growth, in carbohydrate metabolism, in adipocyte maturation, and in the maintenance and development of the immune system. 31 GH also has been shown to enhance the proliferation of human retinal microvascular endothelial cells 32 and of bovine brain capillary endothelial cells, 33 and to promote the formation of capillary-like structures by human umbilical cord vein cells in vitro. 34 In vivo, GH exerts an angiogenic effect in the late-stage chicken-chorioallantoic membrane assay, 35 and transgenic mice expressing bovine GH under the rat phosphoenolpyruvate carboxykinase promoter (bGH tg) show enhanced vascularization of the wound granulation tissue.…”

Human umbilical vein endothelial cells express multiple prolactin isoforms

“…GH stimulates the proliferation of endothelial cells in vitro (Rymaszewky et al 1991) and GH, PRL and placental lactogen induce angiogenesis of quiescent chick embryo capillaries in vivo (Gould et al 1995, Struman et al 1999. This family of hormones also exerts anti-angiogenic effects.…”

Effects of growth hormone in patients with tibial fracture: a randomised, double-blind, placebo-controlled clinical trial

“…In adults, bone remodelling is regulated by a complex interaction of circulating GH, insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs), locally produced IGFs, IGFBPs and other growth factors, acting in an autocrine and paracrine way (22)(23)(24). Stimulation of osteoblasts is believed to be the main mechanism of action (22), but angiogenesis, preservation of muscle tissue and function and improved wound healing may also be involved (25,26).…”