title: Estrogen-like potentiation of ghrelin-stimulated GH secretion by fulvestrant, a putatively selective ER antagonist, in postmenopausal women.
abstract: BACKGROUND
  Hyposomatotropism in healthy aging women reflects in part physiological estrogen (estradiol [E2]) depletion associated with menopause.
  
  
  OBJECTIVE
  The purpose of this study was to test the hypothesis that low concentrations of endogenous E2 after menopause continue to drive GH secretion.
  
  
  METHODS
  The study was performed at the Mayo Center for Clinical and Translational Science.
  
  
  METHODS
  The participants were 24 postmenopausal women (aged 50-77 years with body mass index of 19-32 kg/m(2)).
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled, parallel-cohort treatment study with placebo (PL) (n = 14) or the antiestrogen fulvestrant (FUL) (n = 10) for 3 weeks, followed by infusion of l-arginine with saline, GHRH, ghrelin, or both peptide secretagogues.
  
  
  RESULTS
  GH concentrations were measured over 6 hours with 10-minute sampling and mass spectrometry measures of testosterone, E2, and estrone.
  
  
  RESULTS
  Concentrations of testosterone, E2, estrone, SHBG, IGF-I, LH, and FSH were not influenced by antiestrogen treatment. In contrast, GH rose from 0.096 ± 0.018 (PL) to 0.23 ± 0.063 μg/L (FUL, P = .033), and IGF-I binding protein type 3 (IGFBP-3) from 3.6 ± 0.18 to 4.0 ± 2.0 mg/L (P = .041). Conversely, prolactin fell from 7.1 ± 0.69 (PL) to 5.5 ± 0.57 μg/L (FUL) (P = .05), and IGF-I binding protein type 1 (IGFBP-1) fell from 44 ± 9.4 to 27 ± 4.3 μg/L (P = .048). Moreover, FUL vs PL potentiated mean GH responses to l-arginine/saline (P = .007), l-arginine/ghrelin (P = .008), and l-arginine/GHRH + ghrelin (P = .031), but not l-arginine/GHRH.
  
  
  CONCLUSIONS
  The potent antiestrogen, FUL, amplifies fasting and secretagogue-driven GH secretion and IGFBP-3 concentrations in postmenopausal women without altering SHBG or sex steroid levels. FUL also suppresses prolactin and IGFBP-1, without altering IGF-I. Thus, a major antiestrogen mediates 3 actions of estrogen: agonism (GH), neutral effects (sex steroids), and estrogen antagonism (prolactin and IGFBP-1).
authors.affiliation: Endocrine Research Unit (J.D.V., R.J.Y., J.R.W., D.E., J.C.M.), Mayo Clinic College of Medicine Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905; and Tulane University Health Sciences Center (C.Y.B.), Endocrinology and Metabolism Section, Peptide Research Section, New Orleans, Louisiana 70112.
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Yang
authors.forename: Jean R
authors.initials: JR
authors.lastname: Wigham
authors.forename: Dana
authors.initials: D
authors.lastname: Erickson
authors.forename: John C
authors.initials: JC
authors.lastname: Miles
authors.forename: Cyril Y
authors.initials: CY
authors.lastname: Bowers
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000494:pharmacology; D015331:Cohort Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D054439:Ghrelin / Q000494:pharmacology*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D004965:Estrogen Antagonists; D004967:Estrogens; D054439:Ghrelin; D019382:Human Growth Hormone; D000077267:Fulvestrant; D004958:Estradiol; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine