title: Indirect evidence for decreased hypothalamic somatostatinergic tone in anorexia nervosa.
abstract: OBJECTIVE
  In animals, somatostatin (SRIH) and growth hormone (GH)-releasing hormone (GHRH) increase feeding via a common neural mechanism. Furthermore, SRIH counteracts the suppressive action of corticotrophin-releasing hormone (CRH) on food intake. Hypothetically, SRIH could be involved in the central feeding mechanism in anorexia nervosa (AN). Peripheral administration of pyridostigmine (PD) minimizes the release of hypothalamic SRIH.
  
  
  METHODS
  To study the influence of hypothalamic somatostatinergic inhibition on the exaggerated somatotroph responsiveness to GHRH in patients with severe AN, two GHRH stimulation tests were performed in random order following pretreatment with placebo or PD 2 mg/kg body weight in 13 patients and in 10 age-matched healthy controls. The test procedure was repeated in the patients after weight gain.
  
  
  RESULTS
  In controls, PD potentiated the GHRH-stimulated GH rise but this effect was absent in AN patients. The relative potentiating effect of PD was inversely correlated to cortisol excretion levels and positively correlated to leptin serum levels. After weight gain the relative PD effect increased twofold.
  
  
  CONCLUSIONS
  The pyridostigmine-GHRH responsive pattern points indirectly to greater SRIH withdrawal and greater GHRH release in anorexia nervosa. Moreover, hypothalamic SRIH activity seems to be inversely related to cortisol levels, indirectly supporting the hypothesis that SRIH and CRH neuronal activity are inversely related in anorexia nervosa. Leptin, which is believed to act on hypothalamic feeding mechanisms, seems to be positively related to SRIH activity. Finally, the present data demonstrate that the potentiating effect of pyridostigmine in anorexia nervosa is related to body mass index and increases upon weight gain, suggesting that the low somatostatinergic tone is not primary but is related to the weight loss.
authors.affiliation: Department of Endocrinology and Center for Eating Disorders, Odense University Hospital, DK-5000 Odense, Denmark. rene.k.stoving@dadlnet.dk
authors.forename: R K
authors.initials: RK
authors.lastname: Støving
authors.forename: M
authors.initials: M
authors.lastname: Andersen
authors.forename: A
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: J
authors.initials: J
authors.lastname: Frystyk
authors.forename: J
authors.initials: J
authors.lastname: Hangaard
authors.forename: J
authors.initials: J
authors.lastname: Vinten
authors.forename: O G
authors.initials: OG
authors.lastname: Koldkjaer
authors.forename: C
authors.initials: C
authors.lastname: Hagen
mesh_terms: D000328:Adult; D000856:Anorexia Nervosa / Q000097:blood / Q000503:physiopathology*; D015992:Body Mass Index; D002800:Cholinesterase Inhibitors; D004357:Drug Synergism; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000502:physiology; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D007031:Hypothalamus / Q000503:physiopathology*; D020738:Leptin / Q000097:blood; D011729:Pyridostigmine Bromide; D015430:Weight Gain
chemical_list: D002800:Cholinesterase Inhibitors; D006728:Hormones; D020738:Leptin; D019382:Human Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D011729:Pyridostigmine Bromide