title: Estrogen elevates the peak overnight production rate of acylated ghrelin.
abstract: BACKGROUND
  Acylated ghrelin is the putatively bioactive GH secretagogue.
  
  
  OBJECTIVE
  Estradiol (E2) stimulates the synthesis rather than inhibits the metabolic clearance of acylated ghrelin.
  
  
  METHODS
  The study took place at an academic medical center.
  
  
  METHODS
  Healthy postmenopausal women participated.
  
  
  METHODS
  Interventions included prospectively randomized, double-blind separate-day iv infusions of saline or five graded doses of ghrelin in estrogen-deficient (n=12) and E2-supplemented (n=8) women.
  
  
  RESULTS
  Metabolic clearance rate (MCR), volume of distribution, half-life, and secretion rate of acylated ghrelin were assessed.
  
  
  RESULTS
  In pilot iv bolus ghrelin infusions, the median half-lives of acylated and total ghrelin were 21 and 36 min (P<0.01), MCRs 58 and 8.1 liters/kg.d (P<0.01), and volumes of distribution of 1.0 and 0.32 liters/kg (P<0.01), respectively. Transdermal E2 supplementation for 3 wk increased peak nighttime acylated ghrelin concentrations from 99+/-12 to 141+/-34 pg/ml (P=0.039). Exposure to E2 did not alter the linear relationships between 1) plasma acylated ghrelin concentration and ghrelin infusion rate (638+/-12 slope units), 2) MCR of acylated ghrelin and ghrelin infusion rate (10+/-2.5 slope units), and 3) MCR and plasma concentration of acylated ghrelin (0.017+/-0.004 slope units). These data predict peak nighttime production rates of acylated ghrelin of 3.8+/-0.9 (E2) and 1.9+/-0.2 (no E2) ng/kg.min (P=0.039).
  
  
  CONCLUSIONS
  Acylated ghrelin has a multifold larger distribution volume and MCR than total ghrelin. An estrogenic milieu augments synthesis and/or acylation of ghrelin peptide without altering its MCR.
authors.affiliation: Department of Pediatrics, Endocrine Research Unit, Clinical Translational Research Center, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, Minnesota 55901, USA.
authors.forename: Remberto C
authors.initials: RC
authors.lastname: Paulo
authors.forename: Richard
authors.initials: R
authors.lastname: Brundage
authors.forename: Mihaela
authors.initials: M
authors.lastname: Cosma
authors.forename: Kristi L
authors.initials: KL
authors.lastname: Mielke
authors.forename: Cyril Y
authors.initials: CY
authors.lastname: Bowers
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000215:Acylation; D000328:Adult; D016903:Drug Monitoring; D002149:Energy Intake; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; 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; D007986:Luteinizing Hormone / Q000097:blood; D008657:Metabolic Clearance Rate; D011388:Prolactin / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D055815:Young Adult
chemical_list: D054439:Ghrelin; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone