Human growth hormone and insulin-like growth factor-I inhibit erythropoietin secretion from the kidneys of adult rats

Abstract

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play important roles in erythropoiesis and erythropoietin (EPO) secretion. We examined the effects of GH and IGF-I on EPO production in adult rat kidney and liver in vivo and in vitro. Male Wistar rats aged 8-10 weeks were used. Recombinant human GH (hGH) was continuously infused (20 µg/kg per h) subcutaneously for 48 h using a micro-osmotic infusion pump. Octreotide (10 µg/kg) was subcutaneously injected every 12 h beginning 12 h before the hGH treatment. GH increased plasma EPO levels earlier than it increased plasma IGF-I levels. At 24 h, the IGF-I content in the liver and kidney was increased from 172·8 14·6 to 232·6 17·8 ng/g tissue (means S.E.) and from 53·8 3·1 to 112·8 7·2 ng/g tissue, respectively. The EPO content in the liver was increased from 7·5 1·2 to 15·1 1·4 mIU/g tissue at 48 h, whereas the EPO content in the kidney was decreased at 12, 24, and 48 h after the start of hGH treatment. When the kidneys were organ-cultured, hGH considerably decreased EPO levels in the culture medium in a dose-related manner. The addition of anti-hGH IgG blunted the GH-induced inhibition of EPO secretion from the kidneys. IGF-I also decreased EPO levels in the medium in a dose-related manner. The addition of anti-IGF-I IgG blunted the IGF-I-induced inhibition of EPO secretion from the kidneys, whereas the GH-induced inhibition of EPO secretion was not affected. These findings suggest that both hGH and IGF-I have direct inhibitory effects on EPO secretion from adult rat kidneys.

Effect of Insulin Analogs on the Decline of Hemoglobin in Diabetic Patients with Nephropathy

“…Shamiyo et al [24] showed that administration of human growth hormone to diabetic patients with renal insufficiency and anemia led to an increase in Epo-levels. Similar results have been obtained in animal experiments of the same study group [25] . Quin et al [16] reported on an increase of EPOconcentration after treatment with IGF-1 in a patient with insulin resistance.…”

Hepatic changes of erythropoietin gene expression in a rat model of acute-phase response

“…The authors attributed the lack of haemoglobin production and haematocrit induction to the insufficient levels of circulating iron and to disturbances of the iron metabolism, a typical situation also reported during the APR (5). An induction under normoxic conditions of hepatic EPO in rats has also been described by Sohmiya and Kato (31) after injection of growth hormone. Surprisingly, the authors observed an upregulation of the EPO gene and an increase of the protein content in the livers and plasma of the treated animals with a decrease in renal production.…”

Effects of growth hormone therapeutic supplementation on hematopoietic stem/progenitor cells in children with growth hormone deficiency: focus on proliferation and differentiation capabilities

“…We demonstrated that clonogenic potential of CD34 + -expanded BFU-E was significantly higher in GHD patients treated with GH-RT for 6 months than that before therapy. It is possible that this effect might be a result of the modulatory action of GH on the production of erythropoietin (EPO), as increased concentrations of GH augment the levels of EPO in GHD patients with developed anemia [ 27 , 28 ], possibly due to increased hepatic synthesis of EPO [ 29 ]. However, in in vitro cultures containing an established amount of EPO, we observed increased growth only in the samples collected from patients treated previously with GH-RT.…”