title: The GH-releasing effect of acylated ghrelin in normal subjects is refractory to GH acute auto-feedback but is inhibited after short-term GH administration inducing IGF1 increase.
abstract: OBJECTIVE
  GH secretion is regulated by an interplay between GH-releasing hormone (GHRH), somatostatin (SST), and other central and peripheral signals. Acylated ghrelin (AG) amplifies GH pulsatility acting, at least partially, independently from GHRH and SST. The GH response to GHRH is inhibited by recombinant human GH (rhGH), likely due to a SST-mediated negative GH auto-feedback. The effect of exogenous rhGH on the GH-releasing effect of AG has never been tested.
  
  
  METHODS
  In six healthy volunteers, we studied the GH response to acute AG administration (1.0 μg/kg i.v.) during saline or rhGH infusion (4.0 μg/kg per h i.v.) or after 4-day rhGH (10.0 μg/kg s.c.) administration.
  
  
  RESULTS
  Compared with saline, rhGH infusion increased GH levels (P<0.01). During saline, acute i.v. AG induced a marked increase (P<0.01) in GH levels similar to those observed after AG administration during rhGH infusion. During s.c. rhGH, IGF1 levels rose from day 0 to day 5 (P<0.01). After 4-day s.c. rhGH, i.v. AG increased (P<0.01) GH levels, though significantly (P<0.05) less than on day 0.
  
  
  CONCLUSIONS
  The marked somatotroph-releasing effect of AG is refractory to a direct GH auto-feedback whereas is markedly inhibited after 4-day rhGH administration, suggesting the possibility of a selective IGF1-mediated inhibitory feedback.
authors.affiliation: Division of Endocrinology, Diabetology and Metabolism, Department of Internal Medicine, San Giovanni Battista, Molinette Hospital, University of Turin, Turin, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Benso
authors.forename: E
authors.initials: E
authors.lastname: Gramaglia
authors.forename: I
authors.initials: I
authors.lastname: Olivetti
authors.forename: M
authors.initials: M
authors.lastname: Tomelini
authors.forename: V Ramella
authors.initials: VR
authors.lastname: Gigliardi
authors.forename: S
authors.initials: S
authors.lastname: Frara
authors.forename: E
authors.initials: E
authors.lastname: Calvi
authors.forename: S
authors.initials: S
authors.lastname: Belcastro
authors.forename: D H
authors.initials: DH
authors.lastname: St Pierre
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
authors.forename: F
authors.initials: F
authors.lastname: Broglio
mesh_terms: D000215:Acylation; D000328:Adult; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D054439:Ghrelin / Q000008:administration & dosage*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D054439:Ghrelin; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I