title: Pituitary and/or peripheral estrogen-receptor alpha regulates follicle-stimulating hormone secretion, whereas central estrogenic pathways direct growth hormone and prolactin secretion in postmenopausal women.
abstract: BACKGROUND
  Estradiol (E(2)) stimulates GH and prolactin secretion and suppresses FSH secretion in postmenopausal women. Whether central nervous system (CNS) or pituitary mechanisms (or both) mediate such actions is not known.
  
  
  OBJECTIVE
  Our objective was to distinguish between hypothalamic and pituitary or peripheral (hepatic) actions of E2.
  
  
  METHODS
  This study was performed in an academic medical center.
  
  
  METHODS
  This was a double-blind, prospectively randomized, placebo (Pl)-controlled study.
  
  
  METHODS
  The capability of a selective, noncompetitive, non-CNS permeant estrogen receptor (ER)-alpha antagonist, fulvestrant (FUL) to antagonize the effects of transdermal E2 and Pl on GH, prolactin, and FSH secretion was assessed in 43 women (ages 50-80 yr) in a four parallel-cohort study. Each woman received four secretagogue infusions to stimulate GH secretion. IGF-I and its binding proteins were measured secondarily.
  
  
  RESULTS
  Administration of Pl/E2 increased GH and prolactin concentrations by 100%, and suppressed FSH concentrations by more than 50% (each P<or=0.004 compared with Pl/Pl). Treatment with FUL/E2 compared with Pl/E2 partially relieved estrogen's inhibition of FSH secretion (P=0.041), without altering E2's stimulation of prolactin secretion. ANOVA further revealed that: 1) estrogen milieu (P=0.014) and secretagogue type (P<0.001) each determined GH concentrations; 2) FUL/Pl suppressed IGF-I concentrations (P<0.001); 3) FUL abrogated estrogen's elevation of IGF binding protein-1 concentrations (P<0.001); and 4) FUL did not oppose estrogen's suppression of IGF binding protein-3 concentrations (P<0.001).
  
  
  CONCLUSIONS
  Responses to a non-CNS permeant ERalpha antagonist indicate that E2 inhibits FSH secretion in part via pituitary/peripheral ERalpha, drives prolactin output via nonpituitary/nonperipheral-ERalpha effects, and directs GH secretion and IGF-I-binding proteins by complex mechanisms.
authors: Endocrine Research Unit, Department of Internal Medicine, Mayo Medical and Graduate Schools of Medicine, Mayo Clinic, 200 First Street S.W., Rochester, Minnesota 55905, USA.
authors: Mihaela
authors: M
authors: Cosma
authors: Joy
authors: J
authors: Bailey
authors: John M
authors: JM
authors: Miles
authors: Cyril Y
authors: CY
authors: Bowers
authors: Johannes D
authors: JD
authors: Veldhuis
mesh_terms: D000368:Aged; D001921:Brain / Q000502:physiology*; D004311:Double-Blind Method; D047628:Estrogen Receptor alpha / Q000502:physiology*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism*; D019382:Human Growth Hormone / 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 / Q000032:analysis; D007986:Luteinizing Hormone / Q000378:metabolism; D008875:Middle Aged; D010902:Pituitary Gland / Q000502:physiology*; D017698:Postmenopause / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D011446:Prospective Studies
chemical_list: D047628:Estrogen Receptor alpha; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone