Endocrine Abstracts

Somatostatin inhibits the release of Ghrelin in normal subjects

TMM Tan¹, M Levy², V Skinner³, N Beaumont³, K Srai³, PJ Goadsby², PMG Bouloux¹ & MP Vanderpump¹

¹Department of Endocrinology and Diabetes, Royal Free Hospital School of Medicine, London, UK; ²Headache Group, Institute of Neurology, London, UK; ³Department of Biochemistry and Molecular Medicine, Royal Free Hospital School of Medicine, London, UK.

Ghrelin is a 28 amino acid n-octanoylated peptide which is the natural agonist for the growth hormone secretagogue receptor and which potently stimulates GH release in vivo (1). We studied the effects of a somatostatin infusion on Ghrelin release in normal subjects.

STUDY PROTOCOL

Four females and five males, 25-40 years of age, body mass index < 28 kg per m2 were studied. Local ethics committee permission was obtained for this study. All patients arrived after an overnight fast. Somatostatin (Stilamin, Serono) was infused at a rate of 250 micrograms per hour for 3.5 hours, according to previously published protocols (2). Subjects remained awake, supine and fasted throughout the procedure. No hypoglycaemic episodes were recorded and no adverse effects were observed during or after infusion. Plasma immunoreactive Ghrelin was measured in duplicate with a radioimmunoassay involving an I¹²⁵-labelled bioactive Ghrelin tracer and a rabbit polyclonal antibody against full-length, octanoylated human Ghrelin (Phoenix Pharmaceuticals).

RESULTS

As expected, somatostatin infusion caused suppression of GH levels with maximal suppression seen at 180 mins after the infusion was started (p<0.01, repeated measures one-way ANOVA with Dunnett's multiple comparison test). Interestingly, the Ghrelin levels were also suppressed during somatostatin infusion (p<0.01), with evidence of a rebound in Ghrelin levels after the infusion was terminated.

DISCUSSION

We present data that suggests that somatostatin suppresses Ghrelin release. Di Vito et al. (3) have observed that infusion of somatostatin blunted Ghrelin-stimulated GH release, and mostly abolished GHRH-stimulated GH release. Somatostatin inhibition of GH release therefore seems to proceed via multiple mechanisms, i.e. inhibition of Ghrelin release plus blunting of Ghrelin-stimulated GH release by somatotrophs.

REFERENCES

1. Kojima M et al. Nature. 402:656-660 (1999).

2. Villaume C et al. Biomed Pharmacother 40:61-64 (1986).

3. Di Vito L et al. Clin Endo 56:643-648 (2002).

Endocrine Abstracts (2002) 4 OC4