An inhibition of the hypothalamic somatostatinergic tone is not the cause of the enhanced growth hormone response to growth hormone-releasing hormone in patients with liver cirrhosis.
Animal models of liver cirrhosis (LC) display a reduced hypothalamic somatostatinergic tone. To test whether a similar mechanism could explain the enhanced Growth Hormone (GH) secretory response to GH-Releasing Hormone (GHRH), which is seen in human LC, we studied the effect of the cholinesterase inhibitor pyridostigmine (PD), which is able to reduce the release of hypothalamic somatostatin (SS), on the GHRH-stimulated GH secretion. We considered that if PD were unable to increase GH secretion, this would constitute evidence of an already inhibited endogenous somatostatinergic tone. If proved, this in turn could explain the enhanced GH response to GHRH seen in LC. Ten LC patients and nine controls were given GHRH (100 microg, intravenously), or PD (120 mg, orally) plus GHRH. After GHRH alone, the GH peak was four times higher in LC than in controls (40.85+/-15.7 ng/ml in LC and 9.35+/-2.5 ng/ml in controls). In LC, PD administration markedly increased the GH response to GHRH (GH peak: 98.0+/-19.7 ng/ml; +240% vs. GHRH alone). The ability of PD to increase the GH response in patients with LC suggests that in this condition the enhanced GH response to GHRH is not due to a completely inhibited endogenous somatostatinergic tone. SS appears instead to maintain its modulator role on GH secretion in human LC, in contrast with what observed in animal models.
Fanciulli
G
G
Dipartimento-Struttura Clinica Medica - Patologia Speciale Medica, University of Sassari, Sassari, Italy. gfanciu@uniss.it
Tomasi
P A
PA
Giusti
M
M
Bertoncelli
A
A
Deplano
A
A
Garrucciu
G
G
Delitala
G
G
D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006509:Hepatitis B / Q000473:pathology; D006526:Hepatitis C / Q000473:pathology; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007031:Hypothalamus / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology / Q000473:pathology*; D008297:Male; D010919:Placebos; D016037:Single-Blind Method; D013004:Somatostatin / Q000502:physiology*
D010919:Placebos; D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone