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Insulin-like growth factor-I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats

Authors

  • Inma Castilla-Cortázar,

    Corresponding author
    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • 1,4 M. Aurelia Aliaga-Montilla,

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • 1 Javier Salvador,

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • 2 María García,

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • 1,4 Gloria Delgado,

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • 4 Salvador González-Barón,

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • 4 Jorge Quiroga,

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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  • and 3 Jesús Prieto 3

    1. Departments of 1Human Physiology,2Endocrinology and 3Internal Medicine, Liver Unit, University of Navarra, Pamplona and 4Department of Physiology, School of Medicine, University of Málaga, Spain
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I. Castilla-Cortázar, Department of Physiology, School of Medicine, University of Málaga, 29080 Málaga, Spain.
Tel: 34+52 131577
Fax: 34+52 131650.
e-mail: icastill@uma.es.

Abstract

Abstract:Background/Aims: An altered growth hormone/insulin-like growth factor-I (GH/IGF-I) axis occurs in advanced liver cirrhosis, characterised by diminished serum levels of IGF-I and increased concentrations of GH. Under normal conditions, GH release is mediated by somatostatin (SS) inhibition. However, the influence of SS on GH release in cirrhosis is not well known. IGF-I supplementation has beneficial effects in experimental cirrhosis, and – under physiological conditions – IGF-I increases SS, inhibiting GH. The aims of this work were to study SS tone in cirrhotic animals and to evaluate whether IGF-I treatment influences SS tone, controlling GH secretion in cirrhosis. Methods: We studied the influence of SS on GH secretion by assessing GH response to pyridostigmine (PD) in cirrhotic rats treated and untreated with IGF-I. Liver cirrhosis was induced with CCl4-inhalation for 11 weeks in male Wistar rats. The animals were randomly divided into two groups: CI+IGF (n=12), which received IGF-I treatment for 12 days (2 μg/100 g body wt−1×d−1) and CI (n=12), which received saline. Healthy controls (CO, n=12) were studied at the same time. On day 13, animals from each group were subdivided into two groups (n=6) in order to explore the effect of a PD intrajugular bolus (10 μg×100 gbw−1) on serum GH levels (at 0,10,20,30 and 60 min), which were assessed by RIA. Results: PD bolus did not exert any effect on GH serum levels in the CI group, suggesting a low SS tone in cirrhotic rats. However, PD induced an increase in GH levels into CO and CI+IGF groups. In conclusion, as occurs under normal conditions, the cholinergic system is a significant modulator of GH secretion in experimental liver cirrhosis. Conclusion: Cirrhotic rats have a reduced somatostatinergic tone which can be restored by IGF-I supplementation, suggesting that somatostatin is the main factor involved in the feed-back regulation between GH and IGF-I in cirrhosis.

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