title: Estradiol regulates GH-releasing peptide's interactions with GH-releasing hormone and somatostatin in postmenopausal women.
abstract: OBJECTIVE
  Estrogen stimulates pulsatile secretion of GH, via mechanisms that are largely unknown. An untested hypothesis is that estradiol (E₂) drives GH secretion by amplifying interactions among GH-releasing hormone (GHRH), somatostatin (SS), and GH-releasing peptide (GHRP).
  
  
  METHODS
  The design comprised double-blind randomized prospective administration of transdermal E₂ vs placebo to healthy postmenopausal women (n=24) followed by pulsatile GHRH or SS infusions for 13 h overnight with or without continuous GHRP2 stimulation.
  
  
  METHODS
  End points were mean concentrations, deconvolved secretion, and approximate entropy (ApEn; a regularity measure) of GH.
  
  
  RESULTS
  By generalized ANOVA models, it was observed that E₂ vs placebo supplementation: i) augmented mean (13-h) GH concentrations (P=0.023), GHRH-induced pulsatile GH secretion over the first 3 h (P=0.0085) and pulsatile GH secretion over the next 10 h (P=0.054); ii) increased GHRP-modulated (P=0.022) and SS-modulated (P<0.001) GH ApEn; and iii) did not amplify GHRH/GHRP synergy during pulsatile GH secretion. By linear regression, E₂ concentrations were found to be positively correlated with GH secretion during GHRP2 infusion (P=0.022), whereas BMI was found to be negatively correlated with GH secretion during GHRH (P=0.006) and combined GHRH/GHRP (P=0.015) stimulation. E₂ and BMI jointly determined triple (combined l-arginine, GHRH, and GHRP2) stimulation of GH secretion after saline (R²=0.44 and P=0.003) and pulsatile GHRH (R²=0.39 and P=0.013) infusions.
  
  
  CONCLUSIONS
  In summary, in postmenopausal women, E₂ supplementation augments the amount (mass) and alters the pattern (regularity) of GH secretion via interactions among GHRH, SS, GHRP, and BMI. These outcomes introduce a more complex model of E₂ supplementation in coordinating GH secretion in aging women.
authors.affiliation: Endocrine Research Unit, Mayo School of Graduate Medical Education, Center for Translational Science Activities, Mayo Clinic, Rochester, Minnesota 55905, USA.
authors.forename: Catalina
authors.initials: C
authors.lastname: Norman
authors.forename: Nanette L
authors.initials: NL
authors.lastname: Rollene
authors.forename: Dana
authors.initials: D
authors.lastname: Erickson
authors.forename: John M
authors.initials: JM
authors.lastname: Miles
authors.forename: Cyril Y
authors.initials: CY
authors.lastname: Bowers
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000368:Aged; D001120:Arginine / Q000008:administration & dosage; D015992:Body Mass Index; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D025461:Feedback, Physiological / Q000187:drug effects; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage / Q000378:metabolism*; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism; D050177:Overweight / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017698:Postmenopause; D011673:Pulsatile Flow / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000378:metabolism*; D057968:Transdermal Patch
chemical_list: D009842:Oligopeptides; D019382:Human Growth Hormone; D004958:Estradiol; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; C091874:growth hormone-releasing peptide-2