Endocrine Abstracts (2001) 2 OC11

Systemic and Hypothalamic Actions of Ghrelin in Regulation of Food Intake, Body Weight and Pituitary Function

AM Wren, CJ Small, CR Abbott, LJ Seal, MA Ghatei & SR Bloom

Endocrine Unit, ICSM, Hammersmith, Du Cane Road, London W12 0NN, UK.

Ghrelin, an endogenous growth hormone secretagogue receptor agonist, increases food intake, growth hormone (GH) and adrenocorticotrophic hormone (ACTH) following intracerebroventricular (ICV) and systemic administration. We now show that low dose intraperitoneal (ip) ghrelin (1nmol) stimulates feeding and results in a plasma ghrelin concentration not significantly different to 24-hour fasting levels. Following injection into 8 hypothalamic nuclei, ghrelin (30pmol) potently stimulates food intake in the arcuate nucleus, a site potentially accessible to the circulation (0-1h food intake 427 plus/minus 43% of control, p<0.001 vs control, p<0.01 vs other nuclei). Seven days ip or ICV ghrelin administration increases cumulative food intake (food intake in excess of saline-treated; ip ghrelin 13.6 plus/minus 3.4g, p<0.01; ICV ghrelin 19.6 plus/minus 5.5g, p<0.05). This is associated with excess weight gain (ip ghrelin 21.7 plus/minus 1.4g vs saline 10.6 plus/minus 1.9g, p<0.001; ICV ghrelin 15.3 plus/minus 4.3g vs saline 2.2 plus/minus 3.8g, p<0.05) and adiposity. These data suggest that ghrelin may be important in long-term control of food intake and body weight. Ghrelin stimulates food intake at circulating concentrations found following a fast. This may be via an action on the ARC which is potentially accessible to the circulation.

Using hypothalamic explants in vitro , ghrelin stimulates GH releasing hormone (GHRH) release (basal 18.3 plus/minus 3.5, ghrelin 100nM 39.4 plus/minus 10.7 fmol/explant, p<0.05) but does not affect basal or potassium-stimulated somatostatin release. Ghrelin significantly stimulates corticotrophin releasing hormone (CRH) (basal 4.3 plus/minus 0.5, ghrelin 100nM 6.0 plus/minus 0.8 pmol/explant, p=0.01) and vasopressin (AVP) release (basal 35.0 plus/minus 3.3, ghrelin 100nM 49.2 plus/minus 6.0 fmol/explant, p=0.01). This suggests that ghrelin stimulates GH at least in part via GHRH release but not somatostatin inhibition and ACTH by CRH and AVP release.

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