I. Castilla-cortazar et al., Insulin-like growth factor-I restores the reduced somatostatinergic tone controlling growth hormone secretion in cirrhotic rats, LIVER, 21(6), 2001, pp. 405-409
Background/Aims: An altered growth hormone/insulin-like growth factor-I (GH
/IGF-I) axis occurs in advanced liver cirrhosis, characterised by diminishe
d serum levels of IGF-I and increased concentrations of GH. Under normal co
nditions, GH release is mediated by somatostatin (SS) inhibition. However,
the influence of SS on GH release in cirrhosis is not well known. IGF-I sup
plementation has beneficial effects in experimental cirrhosis, and-under ph
ysiological 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. Met
hods: We studied the influence of SS on GH secretion by assessing GH respon
se to pyridostigmine (PD) in cirrhotic rats treated and untreated with IGF-
I. Liver cirrhosis was induced with CCl4-inhalation for 11 weeks in male Wi
star rats. The animals were randomly divided into two groups: CI + IGF (n=1
2), which received IGF-I treatment for 12 days (2 mug/100 g body wt(-1) x d
(-1)) and CI (n=12), which received saline, Healthy controls (CO, n=12) wer
e studied at the same time. On day 13, animals from each group were subdivi
ded into two groups (n=6) in order to explore the effect of a PD intrajugul
ar bolus (10 mug x 100 gbw(-1)) on serum GH levels (at 0,10,20,30 and 60 mi
n), which were assessed by RIA. Results: PD bolus did not exert any effect
on GH serum levels in the Cl group, suggesting a low SS tone in cirrhotic r
ats. 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 ci
rrhosis.