In rats with sepsis, the acute fall in IGF-I is associated with an increase in circulating growth hormone-binding protein levels

O’Leary, Michael J.; Quinton, Naomi; Ferguson, Colin N.; Preedy, Victor R.; Ross, R. J. M.; Hinds, C. J.

doi:10.1007/s001340000656

Cited by 5 publications

(4 citation statements)

References 23 publications

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“…Furthermore, the low serum IGF‐1 levels might have intensified GH production by a lack of feedback inhibition of pituitary GH secretion 2 . Work by O’Leary and colleagues in rats has shown a trend to increased hepatic GH binding and GH resistance, which was not associated with reduced GH receptor numbers 27 . In our study, the highest GH levels were detected together with the lowest levels of IGF‐1.…”

Section: Discussionsupporting

confidence: 52%

Growth hormone and insulin‐like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

Önenli-Mungan

Yıldızdaş

Yapıcıoğlu

et al. 2004

J Paediatrics Child Health

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There were elevated levels of growth hormone with decreased levels of insulin-like growth factor 1 in children during sepsis and septic shock compared to healthy subjects. In addition, there were even higher levels of growth hormone and lower levels of insulin-like growth factor 1 in non-survivors than in survivors. We think that both growth hormone and insulin-like growth factor 1 may have potential prognostic value to serve as a marker in bacterial sepsis and septic shock in children. As there is insufficient data in the paediatric age group, more studies including large numbers of patients and additionally evaluating cytokines and insulin-like growth factor binding proteins are needed.

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Section: Discussionsupporting

confidence: 52%

Growth hormone and insulin‐like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

Önenli-Mungan

Yıldızdaş

Yapıcıoğlu

et al. 2004

J Paediatrics Child Health

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“…However, an increase in the number of GHRs in the liver has also been reported in septic rats (O'Leary et al 2000).…”

Section: Introductionmentioning

confidence: 92%

“…In rodents, the GH response to LPS or sepsis is more variable than the IGF-I response, since both a decrease (Kasting & Martin 1982, Fan et al 1994, Soto et al 1998 and the absence of modifications (Defalque et al 1999, O'Leary et al 2000 in circulating levels of GH have been described in septic rats. The difference may reside in pulsatile secretion of this hormone.…”

Section: Introductionmentioning

confidence: 99%

Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-I and IGF-binding protein-3 in rats

Priego

Granado²,

Cáceres³

et al. 2003

Journal of Endocrinology

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While it is well known that sepsis inhibits serum IGF-I and its gene expression in the liver, the effect on pituitary GH and IGF-binding protein-3 (IGFBP-3) is poorly understood. The GH-IGF-I-IGFBP-3 response to different doses of lipopolysaccharide (LPS) administration has been investigated in adult male rats. Two experiments were performed, administration of low doses of LPS (5, 10, 50 and 100 µg/kg) and high doses of LPS (100, 250, 500 and 1000 µg/kg). Rats received two i.p. injections of LPS (at 1730 h and 0830 h the following day) and were killed 4 h after the second injection. LPS administration induced a biphasic response in serum concentrations of GH, with an increase at the 10 µg/kg dose, followed by a decrease at higher doses (100 µg/kg on up). Pituitary GH mRNA was also increased by the administration of 10 and 50 µg/kg LPS, whereas at higher doses LPS did not modify pituitary GH mRNA. We also analyzed the GH response to LPS in primary pituitary cell cultures. When exposed to LPS, in the culture medium, there was an increase in GH release at the concentration of 0·1 and 10 ng/ml, whereas more concentrated LPS did not modify GH release. Serum concentrations of IGF-I declined in a dose-dependent fashion after LPS administration in the rats injected with 10 µg/kg LPS on up. This decrease is secondary to modifications in its synthesis in the liver, since endotoxin injection decreased both IGF-I and its mRNA in the liver. The liver GH receptor mRNA was also decreased by LPS administration, but only in the animals injected with high LPS doses. There was a decrease in both the IGFBP-3 serum levels and its gene expression in the liver with all LPS doses studied. These data suggest a biphasic LPS effect on pituitary GH, a stimulatory effect at low doses and an inhibitory effect at higher doses, whereas it has a clear inhibitory effect on IGF-I and IGFBP-3 synthesis in the liver. The decrease in liver IGFBP-3 mRNA and in serum concentrations of IGFBP-3 in the rats injected with LPS may contribute to the decrease in serum concentrations of IGF-I.

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“…The effect of sepsis on GHRs remains uncertain. After CLP both increased specific binding of GH to the liver [ 29 ] and reduced expression of hepatic mRNA of GHRs have been demonstrated [ 14 ]. Reduced receptor binding and mRNA was found following endotoxin challenge [ 30 ], whilst unchanged GHR mRNA was demonstrated after fecal agar pellet implantation [ 13 ].…”

Section: Discussionmentioning

confidence: 99%

Parenteral versus enteral nutrition: effect on serum cytokines and the hepatic expression of mRNA of suppressor of cytokine signaling proteins, insulin-like growth factor-1 and the growth hormone receptor in rodent sepsis

O’Leary

Xue²,

Scarlett³

et al. 2007

Crit Care

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Introduction Early nutrition is recommended for patients with sepsis, but data are conflicting regarding the optimum route of delivery. Enteral nutrition (EN), compared with parenteral nutrition (PN), results in poorer achievement of nutritional goals but may be associated with fewer infections. Mechanisms underlying differential effects of the feeding route on patient outcomes are not understood, but probably involve the immune system and the anabolic response to nutrients. We studied the effect of nutrition and the route of delivery of nutrition on cytokine profiles, the growth hormone-insulin-like growth factor-1 (IGF-I) axis and a potential mechanism for immune and anabolic system interaction, the suppressors of cytokine signaling (SOCS), in rodents with and without sepsis.

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In rats with sepsis, the acute fall in IGF-I is associated with an increase in circulating growth hormone-binding protein levels

Abstract: Reduced IGF-I levels in sepsis in the rat are associated with elevations in GHBP and a trend to increased hepatic GH binding. This suggests that in sepsis 'GH resistance' is not associated with reduced GH receptor numbers.

Cited by 5 publications

References 23 publications

Growth hormone and insulin‐like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

Growth hormone and insulin‐like growth factor 1 levels and their relation to survival in children with bacterial sepsis and septic shock

Endotoxin at low doses stimulates pituitary GH whereas it decreases IGF-I and IGF-binding protein-3 in rats

Parenteral versus enteral nutrition: effect on serum cytokines and the hepatic expression of mRNA of suppressor of cytokine signaling proteins, insulin-like growth factor-1 and the growth hormone receptor in rodent sepsis

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