title: The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state.
abstract: OBJECTIVE
  Ghrelin, a gastric-derived natural ligand of the GH secretagogue (GHS)-receptor (GHS-R), strongly stimulates GH secretion but also possesses other neuroendocrine actions, stimulates food intake and modulates the endocrine pancreas and energy homeostasis. Ghrelin secretion is negatively modulated by food intake. Similarly, glucose and also insulin probably exert an inhibitory effect on ghrelin secretion. Fasting ghrelin levels are reduced in obesity, elevated in anorexia nervosa and restored by weight recovery. The chronic elevation of circulating ghrelin levels in anorexia suggested the hypothesis of an alteration of the sensitivity to the orexigenic action of ghrelin in this condition. The aim of this study was to define the endocrine actions of ghrelin in patients with anorexia nervosa.
  
  
  METHODS
  We enrolled nine women with anorexia nervosa of restricter type [AN; age (mean +/- SEM) 24.2 +/- 1.8 years; body mass index (BMI) 14.7 +/- 0.4 kg/m2] and seven normal young women in their early follicular phase as control group (NW; age 30.6 +/- 3.1 years; BMI 20.3 +/- 0.5 kg/m2).
  
  
  METHODS
  In all the subjects we studied the GH, PRL, ACTH, cortisol, insulin and glucose responses to acute ghrelin administration (1.0 microg/kg as i.v. bolus). The GH response to GHRH (1.0 microg/kg as i.v. bolus) and basal ghrelin and IGF-I levels were also evaluated in all the subjects.
  
  
  RESULTS
  Basal morning ghrelin and GH levels in AN (643.6 +/- 21.3 ng/l and 10.4 +/- 0.5 microg/l, respectively) were higher (P < 0.05) than in NW (233.5 +/- 14.2 ng/l and 0.7 +/- 0.7 microg/l, respectively). However, IGF-I levels in AN (145.3 +/- 10.9 microg/l) were lower (P < 0.05) than in NW (325.4 +/- 12.6 microg/l). The GH response to GHRH in AN was higher (P < 0.05) than that in NW, but in AN the GH response to ghrelin was lower (P < 0.05) than that in NW. In AN and NW ghrelin also induced similar increases (P < 0.05) in PRL, ACTH and cortisol levels. Ghrelin administration was followed by significant increase in glucose levels in NW (P < 0.05) but not in AN.
  
  
  CONCLUSIONS
  This study demonstrates that anorexia nervosa, a clinical condition of ghrelin hypersecretion, shows a specific reduction in the GH response to ghrelin, despite the hyper-responsiveness to GHRH administration. The impaired GH response to ghrelin in anorexia nervosa agrees with previous evidence of blunted GH response to synthetic GH secretagogues and could reflect desensitization of the GHS receptor induced by the chronic elevation of ghrelin levels in this pathological state.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Erasmus University, Rotterdam, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Broglio
authors.forename: L
authors.initials: L
authors.lastname: Gianotti
authors.forename: S
authors.initials: S
authors.lastname: Destefanis
authors.forename: S
authors.initials: S
authors.lastname: Fassino
authors.forename: G
authors.initials: G
authors.lastname: Abbate Daga
authors.forename: V
authors.initials: V
authors.lastname: Mondelli
authors.forename: F
authors.initials: F
authors.lastname: Lanfranco
authors.forename: C
authors.initials: C
authors.lastname: Gottero
authors.forename: C
authors.initials: C
authors.lastname: Gauna
authors.forename: L
authors.initials: L
authors.lastname: Hofland
authors.forename: A J
authors.initials: AJ
authors.lastname: Van der Lely
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D000704:Analysis of Variance; D000856:Anorexia Nervosa / Q000097:blood / Q000503:physiopathology*; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D005260:Female; D054439:Ghrelin; D013007:Growth Hormone-Releasing Hormone; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D036361:Peptide Hormones / Q000097:blood; D011388:Prolactin / Q000097:blood; D018709:Statistics, Nonparametric
chemical_list: D001786:Blood Glucose; D054439:Ghrelin; D007328:Insulin; D036361:Peptide Hormones; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D011388:Prolactin; D013007:Growth Hormone-Releasing Hormone; D006854:Hydrocortisone