title: Estradiol potentiates ghrelin-stimulated pulsatile growth hormone secretion in postmenopausal women.
abstract: BACKGROUND
  Ghrelin and an estrogen-rich milieu individually amplify pulsatile GH secretion by increasing the amount of hormone released per burst. However, how these distinct agonists interact in controlling pulsatile GH output is not known.
  
  
  OBJECTIVE
  The objective of the study was to test the hypothesis that elevated estradiol (E(2)) concentrations potentiate hypothalamo-pituitary responses to a near-physiological ghrelin stimulus.
  
  
  METHODS
  This was a double-blind, placebo-controlled, prospectively randomized, parallel-cohort study.
  
  
  METHODS
  The study was conducted at an academic medical center.
  
  
  METHODS
  Twenty-one postmenopausal women participated in the study.
  
  
  METHODS
  Eleven subjects received placebo (Pl) and 10 others E(2) transdermally in escalating doses over 3 wk to mimic late follicular-phase E(2) concentrations. Saline or a submaximally stimulatory amount of ghrelin (0.3 microg/kg) was infused iv on separate randomly ordered mornings fasting after 17-21 d of Pl or E(2) administration.
  
  
  RESULTS
  Outcomes included serum concentrations of E(2), ghrelin, GH, IGF-I, IGF binding protein (IGFBP)-1 and IGFBP-3, and the estimated mass and waveform of stimulated GH secretory bursts.
  
  
  RESULTS
  Administration of E(2) yielded late follicular-phase E(2) concentrations. Compared with Pl, E(2) did not alter ghrelin concentrations but reduced IGF-I and IGFBP-3 and elevated IGFBP-1 concentrations. Compared with saline, ghrelin infusion amplified pulsatile GH secretion by 7.1-fold (P < 0.01). The effect of E(2) alone was 2.0-fold placebo and that of combined ghrelin/E(2) 10.4-fold (P < 0.01). Ghrelin and E(2) accelerated initial GH release individually but nonadditively by more than 2-fold (P < 0.01).
  
  
  CONCLUSIONS
  Estrogen augments ghrelin's near-physiological stimulation of pulsatile GH secretion and mimics ghrelin's acceleration of initial GH release. Thus, we hypothesize that estrogen and a GH secretagogue act via independent as well as convergent mechanisms.
authors.affiliation: Endocrine Research Unit, Department of Internal Medicine, Mayo School of Graduate Medical Education, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Keenan
authors.forename: Ali
authors.initials: A
authors.lastname: Iranmanesh
authors.forename: Kristi
authors.initials: K
authors.lastname: Mielke
authors.forename: John M
authors.initials: JM
authors.lastname: Miles
authors.forename: Cyril Y
authors.initials: CY
authors.lastname: Bowers
mesh_terms: D000368:Aged; D015331:Cohort Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D054439:Ghrelin; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood / Q000494:pharmacology*; D017698:Postmenopause / Q000187:drug effects / Q000502:physiology*
chemical_list: D054439:Ghrelin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D036361:Peptide Hormones; D019382:Human Growth Hormone; D004958:Estradiol; D007334:Insulin-Like Growth Factor I