Plasma growth hormone-binding activity is low in uraemic children

Postel-Vinay, Marie-Catherine; Tar, Attila; Crosnier, H.; Broyer, M.; Rappaport, R; Tönshoff, Burkhard; Mehls, Otto

doi:10.1007/bf01453698

Cited by 81 publications

(25 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While the corollary to this is shortened half-life and accelerated clearance of IGF-1, decreased levels of IGF-1 may also be due to reduced hepatic synthesis through downregulation of the GH receptor [11,13] . As GH-binding protein is generated from proteolytic cleavage of the GH receptor, low levels of GHBP in GH-resistant states consequent to chronic inflammation provide surrogate evidence for a GH receptor defect in children [19] . By downregulating GH-induced expression of the GH receptor gene in hepatocytes in vitro, IL-1 and TNF-␣ are also implicated in the dysregulation of the GH-IGF-1 system [20] .…”

Section: Chronic Inflammationmentioning

confidence: 99%

Growth and Chronic Disease

Patel¹

2007

Ann Nestlé [Engl]

View full text Add to dashboard Cite

Growth impairment occurs with many chronic conditions. Cystic fibrosis, Crohn’s disease and juvenile idiopathic arthritis are relatively common chronic diseases in childhood associated with substantial growth impairment. While growth failure may be the initial presenting feature of pathology, the pattern of growth is also a useful measure of disease severity and response to treatment. In addition to its diagnostic value, the resulting short stature cannot only be unacceptable to patients but can also have detrimental effects on the physical health of patients with conditions such as cystic fibrosis. Growth impairment in children with chronic disease is associated with disruption of the growth hormone (GH)–insulin-like growth factor (IGF) axis, and predominantly results from undernutrition, chronic inflammation and prolonged corticosteroid treatment. Undernutrition leads to major adaptations in the endocrine system geared towards conserving energy, diverting substrates away from growth and reproduction, and providing alternative sources of energy for critical body homeostasis. Although chronic inflammatory processes exacerbate undernutrition, proinflammatory cytokines such as interleukin-6, tumor necrosis factor-α and interleukin-1β also adversely affect growth, independent of nutrition, by disrupting the integrity of the GH–IGF axis and by direct local effects on growth plate chondrogenesis. These growth-regulating mechanisms are disturbed further by corticosteroids used in some chronic conditions for their anti-inflammatory and immunosuppressive properties. It is likely that the growth-suppressing processes slow growth plate senescence, and this in turn enables catch-up growth on recovery from chronic disease and withdrawal of corticosteroid treatment. Trials of recombinant human GH (rhGH) in patients with growth failure suggest improvement in linear growth as well as beneficial effects on body composition and clinical course. These have been of relatively short duration, and long-term benefits as well as the safety of rhGH need to be evaluated particularly when given concomitantly with corticosteroids.

show abstract

Section: Chronic Inflammationmentioning

confidence: 99%

Growth and Chronic Disease

Patel¹

2007

Ann Nestlé [Engl]

View full text Add to dashboard Cite

show abstract

“…In elderly nonuremic humans, recombinant human GH (rhGH) stimulates osteocalcin, hydroxyproline and PTH secretion [113], while in GH-deficient adults, only osteocalcin is stimulated [114]. While GH levels are increased in uremia [115, 116], GH receptor expression is reduced [117], causing reduced hepatic synthesis of IGF-1. rhGH treatment of uremic children accelerates growth, and also increases PTH and alfacalcidol requirements [118, 119].…”

Section: A Nutritional Disorder?mentioning

confidence: 99%

Causes and Consequences of Adynamic Bone Disease

Heaf¹

2001

Nephron

View full text Add to dashboard Cite

“…IGFBP-2 was increased two- to threefold as in uremic children [25]. Hormonal treatments per se did not change the pattern of IGFBP, but increased free IGF-1 concentrations, hence leading to growth improvement [2, 3, 8]. …”

Section: Discussionmentioning

confidence: 99%

“…GH insensitivity, reduced production of the growth mediator IGF-1, diminished IGF-1 bioactivity may all take part in the pathomechanism [1, 2, 3, 4, 5, 6]. …”

Section: Introductionmentioning

confidence: 99%

Hypoglycemic Effects of Insulin-Like Growth Factor-1 in Experimental Uremia: Can Concomitant Growth Hormone Administration Prevent This Effect?

et al. 1999

Self Cite

View full text Add to dashboard Cite

The risk of hypoglycemia limits the clinical application of insulin-like growth factor-1 (IGF-1). Our studies aimed to evaluate the mode of occurrence as well as the prevention of this side effect. Acute administration (i.v. infusion) of IGF-1 in subtotal nephrectomized uremic (U), sham-operated ad libitum fed control (C) and sham-operated pair-fed control (P) rats led to hypoglycemia, though more expressed in P. Serum glucose levels decreased within 60 min after the IGF-1 administration by 40% in U, by 45% in C and by 52% in P (p < 0.05, U vs. P). Chronic administration (7 days) of 1, 4 and 8 mg/kg/day IGF-1 in U rats led to hypoglycemia in an increasing manner as the dose of IGF-1 increased. On the first day, 2 h after injection, serum glucose levels were 116.5 ± 8.6, 110.4 ± 12.4, 60,3 ± 19.2 and 50.6 ± 18.3 mg/dl, respectively (p < 0.01). One week later, IGF-1 therapy proved to be less hypoglycemic in all the groups. On day 7, 2 h after injection the serum glucose levels were 118.9 ± 23.8, 89.0 ± 23.9 and 66.0 ± 32.0, respectively (in comparison to day 1 for 4 and 8 mg/kg/day IGF-1 p < 0.05). The combined effect of 4 mg/kg/day IGF-1 and 10 IU/kg/day growth hormone (GH) was also studied in U and P animals. Two hours after the first injections of IGF-1 serum glucose levels decreased in U from 120.0 ± 11.3 to 49.2 ± 21.6 mg/dl, while IGF-1 plus GH decreased the glucose level from 122.0 ± 15.5 to 81.3 ± 24.7 mg/dl (p < 0.05 IGF-1 vs. IGF-1 + GH). The hypoglycemic effect of IGF-1 was less expressed by long-term treatment and simultanous administration of GH overcame the glucose-lowering effect of IGF-1 (serum glucose levels on day 11 one hour after the injections: 73.7 ± 15.3 mg/dl with IGF-1, and 111.0 ± 7.8 mg/dl with IGF-1 + GH). Methylprednisolone (MP) did not significantly alter the former effects of IGF-1 and GH. In summary, IGF-1 leads to hypoglycemia in control and uremic rats in a dose-dependent manner. This effect becomes less expressed after prolonged administration. GH attenuates the hypoglycemic effect of IGF-1. This suggests that the combined GH and IGF-1 treatment is more effective and less dangerous in correcting uremic growth failure.

show abstract

Plasma growth hormone-binding activity is low in uraemic children

Cited by 81 publications

References 14 publications

Growth and Chronic Disease

Growth and Chronic Disease

Causes and Consequences of Adynamic Bone Disease

Hypoglycemic Effects of Insulin-Like Growth Factor-1 in Experimental Uremia: Can Concomitant Growth Hormone Administration Prevent This Effect?

Contact Info

Product

Resources

About