Human growth hormone and insulin-like growth factor-I inhibit erythropoietin secretion from the kidneys of adult rats
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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play important roles in erythropoiesis and erythro-poietin (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.Keywords:
Somatomedin
While it has been suggested that orally transmitted erythropoietin can stimulate erythropoiesis, in vitro studies have shown that this glycoprotein is inactivated by incubation with various proteolytic enzymes. This study, utilizing the incorporation of 59 Fe in the plethoric mouse, suggests that orally administered erythropoietin is ineffective in stimulating erythropoiesis.
Proteolytic enzymes
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Progress is reported in studies directed toward an understanding of the mechanism of control of red blood cell formation. A relatively rapid and sensitive method of assay for erythropoietin was developed, using the rate of incorporation of iron-59 into the red cells of normal, hypophysectomized, or starved rats as a measure of the rate of erythropoiesis. Factors that control erythropoiesis through control of production of erythropoietin were studied. The effect of erythropoietin in initiating marrow activity was demonstrated in mice having a completely suppressed marrow as far as red cell formation is concerned. Data are reported from studies on the effect of cobalt in polycythemia, the site of erythropoietin production, the clinical significance of erythropoietin, the production of erythropoietin by fetuses in utero, the effect of erythropoietin on iron absorption, and the properties of erythropoietin isolated from plasma. A list of publications during the period is included. (C.H.)
Red Cell
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ABSTRACT. The regulation of erythropoiesis during the first three months of life was studied in 30 premature infants who had haemoglobin concentrations which were lower than in term infants of the same postdelivery age. Erythropoietin and erythropoiesis inhibitors were measured by means of an exhypoxic polycythaemic mouse bioassay. The percentage of haemoglobin F was determined as well. An increased erythropoietin level was detected only in six infants older than six weeks, whose blood haemoglobin concentration was lower than 100 g/l, while in serum from other babies erythropoietin was undetectable by the method used. Erythropoiesis inhibitors were present in 80% of the samples tested. The results presented indicate that in premature infants erythropoiesis is regulated through erythropoietin and that inhibitors of erythropoiesis take part in this regulation as well, but that the haemoglobin level at which erythropoietin is increased is lower in preterm infants than in term babies.
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While it has been suggested that orally transmitted erythropoietin can stimulate erythropoiesis, in vitro studies have shown that this glycoprotein is inactivated by incubation with various proteolytic enzymes. This study, utilizing the incorporation of 59Fe in the plethoric mouse, suggests that orally administered erythropoietin is ineffective in stimulating erythropoiesis.
Proteolytic enzymes
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We found primary erythrocytosis in two male siblings with hematologically normal parents. To clarify the abnormalities in erythropoiesis, we studied erythropoietin production in the older sibling as well as in vivo and in vitro responses of bone marrow to various stimuli. His erythropoietin excretion after a 1000-ml phlebotomy increased by 0 to 11 units per day. In liquid-suspension culture, erythropoiesis was prominently augmented by erythropoietin and unstimulated erythropoiesis was greater and more prolonged than normal. Numbers of erythroid colonies rose in methylcellulose culture without exogenous erythropoietin, and cloning increased with added erythropoietin. Anti-erythropoietin antibody substantially decreased erythropoiesis in vitro. Increased bone-marrow erythropoiesis was also demonstrated in murine diffusion chambers. The principal abnormality in this familial erythrocytosis appears to be a greatly expanded erythropoietic precursor pool that is responsive to erythropoietin in vitro and in vivo. This abnormality is analogous to the functional erythropoietic defect in typical polycythemia vera.
Ineffective erythropoiesis
Phlebotomy
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Abstract Erythropoiesis was obtained in murine long‐term bone‐marrow cell cultures (LTBMCs) in the presence of erythropoietin (Epo) when the medium was frequently renewed. The level of the erythropoietic differentiation was shown to be a function of the erythropoietin concentration. In response to Epo addition, an activity which stimulates CFU‐E proliferation in semisolid cultures of fresh bone marrow cells was detected in the LTBMC supernatants. These results suggest that another factor, whose synthesis may be under Epo control, participates in the stimulation of erythropoiesis in vitro.
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Reticulocyte
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The injection of testosterone into polycythemic mice produces a small but significant stimulation of erythropoiesis, as measured by Fe59 uptake into the peripheral blood, if the interval between the injection of the hormone and Fe59 is 96 hours. This stimulation of erythropoiesis is completely abolished by the injection of immune serum against the hormone erythropoietin.
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