Stimulation of erythropoietin secretion by continuous subcutaneous infusion of recombinant human GH in anemic patients with chronic renal failure

Sohmiya, Motoi; Ishikawa, Kimiko; Kato, Yuzuru

doi:10.1530/eje.0.1380302

Cited by 27 publications

(28 citation statements)

References 37 publications

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“…24 Thus, FSH would be the first pituitary hormone able to increase Epo mRNA expression in in vitro conditions, although GH has been previously shown to stimulate Epo secretion in anemic patients with chronic renal failure. 25 These results, together with the previous description of specific binding sites in Leydig cells, suggest that Epo may play a yet unknown local regulatory role in testis. It is tempting to speculate that testis could respond to specific stimuli with an increased local production of Epo that would stimulate Leydig cell steroidogenesis or could act inside the seminiferous tubule.…”

Section: Resultssupporting

confidence: 60%

Erythropoietin expression in primary rat Sertoli and peritubular myoid cells

Magnanti

Gandini

Giuliani

et al. 2001

Blood

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16 The widespread distribution of Epo mRNA and functional Epo receptors has suggested that Epo may act as a paracrine factor. In testis there is a consistent basal expression of Epo mRNA, and hypoxic exposure leads to increased levels of the transcript in the whole organ, 2,6 but the identity of Epo-producing cells in testis is not defined. However, it has been observed that Epo influences rat Leydig cell steroidogenesis in vitro by stimulating testosterone production through a specific receptor-mediated mechanism 17 ; furthermore, in humans, intravenous Epo administration increases testosterone production. 18 In the present study, we examined by means of competitive reverse transcriptase-polymerase chain reaction (RT-PCR) whether rat Sertoli, Leydig, and peritubular myoid primary cell cultures express Epo mRNA. Our results revealed that Epo mRNA is expressed in Sertoli and peritubular myoid cells. Study design AnimalsTwenty-day-old male Sprague Dowley rats (Charles-River, Como, Italy) were killed by decapitation, and testes and kidneys were removed, frozen in liquid nitrogen, and stored at Ϫ70°C until RNA extraction. Cell culturesPrimary Sertoli and peritubular myoid cells were isolated from 20-day-old rat testes by sequential enzymatic digestion with a previously described procedure. 19 Sertoli cell clusters were resuspended in Dulbecco modified Eagle medium/F-12 medium (1:1) (Gibco, Paisley, United Kingdom), plated, and maintained at 34°C under humidified atmosphere with 5% CO 2 . On day 3, plates were exposed to a hypotonic to remove contaminating germ cells. Contamination with peritubular cells, as assessed by staining for alkaline phosphatase, was negligible (1%-2%), and contamination with Leydig cells, evaluated by cytochemical detection of 3␤-hydroxysteroid dehydrogenase activity, was virtually absent.Purified peritubular myoid cells were separated from Sertoli cells by a Percoll discontinuous gradient technique. 20 Primary cultures of peritubular myoid cells were maintained at 34°C in 5% CO 2 atmosphere in Dulbecco modified Eagle medium/F12 (1:1) containing 10% fetal calf serum (Gibco). Cell purity, never below 97%, was evaluated by alkaline phosphatase activity on adherent cells.After 4 days, Sertoli cells were incubated with either 100 ng/mL ovine follicle-stimulating hormone (o-FSH-17; NIH, Bethesda, MD), 1 M testosterone (Sigma, St Louis, MO), or 100 M CoCl 2 for 18 hours. Between day 10 and 12, peritubular myoid cells were treated with 1 M testosterone and 100 M CoCl 2 for 18 hours in 95% air and 5% CO 2 . After exposure to stimuli, Sertoli and peritubular myoid cells were harvested for total RNA extraction.Leydig cell-enriched cultures and the rat tumor Leydig cell line LC-540, obtained from American Type Culture Collection, were prepared and cultured using previously described procedures. 21,22 After 48 hours of cultures, Leydig cells, whose purity was never below 88% as assessed by cytochemical detection of 3␤-hydroxysteroid dehydrogenase, and LC-540 cells were harvested for RNA extraction.Cell...

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Section: Resultssupporting

confidence: 60%

Erythropoietin expression in primary rat Sertoli and peritubular myoid cells

Magnanti

Gandini

Giuliani

et al. 2001

Blood

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“…EPO secretion is controlled mainly by oxygen pressure (Koury et al 1988, Eckardt et al 1989. We previously reported that plasma EPO levels increased after the start of rhGH infusion in anemic patients with chronic renal failure (Sohmiya et al 1998) and in adult patients with GH deficiency (Sohmiya & Kato 2001). Human plasma EPO levels increased within 6 h after the start of rhGH administration, suggesting that GH directly stimulates EPO production.…”

Section: Discussionmentioning

confidence: 99%

“…Although GH has a stimulatory effect on erythropoiesis, there have been few reports on the role of GH in EPO secretion. We previously reported that GH treatment increased plasma EPO levels in anemic patients with diabetic nephropathy (Sohmiya et al 1998) and in patients with GH deficiency (Sohmiya & Kato 2001). EPO is secreted from various organs depending on various conditions.…”

Section: Introductionmentioning

confidence: 99%

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

Sohmiya

Kato²

2005

Journal of Endocrinology

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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.

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“…80 The fact that the rise in plasma Epo occurred earlier than the rise in insulin-like growth factor-1 (IGF-1) indicates that GH directly stimulates Epo production. IGF-1 was earlier shown to promote the growth of erythrocytic progenitors.…”

Section: Other Erythropoietic Hormonesmentioning

confidence: 99%

Blood doping and its detection

Jelkmann

Lundby

2011

Blood

127

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Hemoglobin mass is a key factor for maximal exercise capacity. Some athletes apply prohibited techniques and substances with intent to increase hemoglobin mass and physical performance, and this is often difficult to prove directly. Autologous red blood cell transfusion cannot be traced on reinfusion, and also recombinant erythropoietic proteins are detectable only within a certain timeframe. Novel erythropoietic substances, such as mimetics of erythropoietin (Epo) and activators of the Epo gene, may soon enter the sports scene. In addition, Epo gene transfer maneuvers are imaginable. Effective since December 2009, the World Anti-Doping Agency has therefore implemented “Athlete Biologic Passport Operating Guidelines,” which are based on the monitoring of several parameters for mature red blood cells and reticulocytes. Blood doping may be assumed, when these parameters change in a nonphysiologic way. Hematologists should be familiar with blood doping practices as they may play an important role in evaluating blood profiles of athletes with respect to manipulations, as contrasted with the established diagnosis of clinical disorders and genetic variations.

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Stimulation of erythropoietin secretion by continuous subcutaneous infusion of recombinant human GH in anemic patients with chronic renal failure

Cited by 27 publications

References 37 publications

Erythropoietin expression in primary rat Sertoli and peritubular myoid cells

Erythropoietin expression in primary rat Sertoli and peritubular myoid cells

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

Blood doping and its detection

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