Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment

Edmondson, Stephanie R.; Baker, Naomi L.; Oh, Jun; Kovàcs, Gabór; Werther, George A.; Mehls, Otto

doi:10.1046/j.1523-1755.2000.00141.x

Cited by 44 publications

(30 citation statements)

References 39 publications

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“…However, an increased growth plate cartilage height has not been consistently found in uremic rats. Uremic growth plate size greater than [1,6,9,11,12,14], similar to [2,4,5,8,10,11,13,14] or even smaller than [7,8] that of control animals has been reported. The reasons for this disparity are unknown.…”

Section: Introductionmentioning

confidence: 72%

“…Several studies have analyzed the tibial growth plate of young uremic rats in an attempt to clarify the mechanisms underlying growth impairment in chronic renal failure [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. There is interest in studying the growth plate in this animal model because this is where longitudinal growth takes place and it cannot be studied in children.…”

Section: Introductionmentioning

confidence: 99%

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Growth plate height of uremic rats is influenced by severity and duration of renal failure

Fernández-Fuente

Santos

Carbajo-Pérez

et al. 2004

Pediatric Nephrology

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To understand the changes induced by uremia in the epiphyseal growth plate, two studies were performed in young rats. In study 1, the morphological features of the tibial growth cartilage of stunted rats with different degrees of reduction of renal function were analyzed 2 weeks after nephrectomy and compared with control rats. There was a negative ( r=-0.549, P<0.05) correlation between serum urea nitrogen (SUN) concentrations and longitudinal growth rate. The heights (mean+/-SEM) of growth cartilage (564+/-32 vs. 366+/-9 microm) and its hypertrophic zone (321+/-25 vs. 157+/-6 microm) were greater ( P<0.05) in uremic than control rats and were highly and positively correlated ( r=0.604, P<0.03 and r=0.706, P<0.01) with SUN levels. In study 2, the time course of growth plate alterations was investigated in uremic rats sacrificed 1 (NX-1), 2 (NX-2), and 4 weeks (NX-4) after nephrectomy compared with their corresponding control animals (C-1, C-2, C-4). Growth cartilage and hypertrophic zone heights were greater in NX-2 (533+/-60 and 264+/-32 microm) than in C-2 (345+/-10 and 131+/-11 microm), with no significant differences in the other groups. This report shows that enlargement of the growth plate and its hypertrophic stratum is greatly, although not exclusively, influenced by the severity and duration of renal insufficiency.

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Section: Introductionmentioning

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Growth plate height of uremic rats is influenced by severity and duration of renal failure

Fernández-Fuente

Santos

Carbajo-Pérez

et al. 2004

Pediatric Nephrology

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“…Growth responses of uremic chondrocytes were reduced to GH and IGF-I specifically, since growth responses to fibroblast growth factor and transforming growth factor were normal [57]. A study of uremic rats showed a reduction in GHR density in tibial growth plate [58] and low levels of mRNA for hepatic GH receptor [59]. In addition, there is evidence from animal studies that IGF-I resistance also arises from tissue insensitivity caused by a post-receptor defect in IGF-I-mediated signal transduction [60], although the site of the abnormality is controversial [61].…”

Section: Gh-igf-i Insensitivity and Growth Failure In Ckdmentioning

confidence: 99%

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

Mak

Cheung

Roberts

2008

Growth Hormone & IGF Research

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Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are important physiologic regulators of growth, body composition, and kidney function. Perturbations in the GH-IGF-I axis are responsible for many important complications seen in chronic kidney disease (CKD), such as growth retardation and cachectic wasting, as well as disease progression. Recent evidence suggests that CKD is characterized by abnormalities in GH and IGF-I signal transduction and the interaction of these pathways with those that involve other molecules such as ghrelin, myostatin, and the suppressor of cytokine signaling (SOCS) family. Further understanding of GH/IGF pathophysiology in CKD may lead to the development of therapeutic strategies for these devastating complications, which are associated with high rates of mortality and morbidity.

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“…Some reports have described reduced hepatic GHR mRNA and growth plate GHR protein levels in rats with CRF [28,29]. Other animal studies have suggested that the receptor protein levels are unaltered by uremia per se [25,26,27], but that reduced food intake is the cause of the GHR changes [25,30].…”

Section: Alterations In Gh Receptor Expressionmentioning

confidence: 99%

Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling

et al. 2005

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Resistance to growth hormone (GH) is a significant complication of advanced chronic renal failure. Thus while the circulating GH levels are normal or even elevated in uremia, resistance to the hormone leads to stunting of body growth in children and contributes to muscle wasting in adults. Insensitivity to GH is the consequence of multiple defects in the GH/insulin-like growth factor-1 (IGF-1) system. Expression of the GH receptor may be reduced, although this is not a consistent finding, GH activation of the Janus kinase 2-signal transducer (JAK2) and activator of transcription (STAT) signal transduction pathway is depressed and this leads to reduced IGF-1 expression, and finally there is resistance to IGF-1, a major mediator of GH action. We review these various defects with an emphasis on the GH-activated JAK2-STAT5 pathway, since this pathway is essential for normal body growth and there has been recent progress in our understanding of the perturbations that occur in uremia.

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Growth hormone receptor abundance in tibial growth plates of uremic rats: GH/IGF-I treatment

Abstract: These studies point to a mechanism for the growth retardation seen in children with CRF, and suggest that combined GH/IGF-I treatment may provide more effective therapy for these patients than GH alone.

Cited by 44 publications

References 39 publications

Growth plate height of uremic rats is influenced by severity and duration of renal failure

Growth plate height of uremic rats is influenced by severity and duration of renal failure

The growth hormone–insulin-like growth factor-I axis in chronic kidney disease

Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling

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