title: Testosterone supplementation in older men restrains insulin-like growth factor's dose-dependent feedback inhibition of pulsatile growth hormone secretion.
abstract: BACKGROUND
  Pulsatile GH secretion declines in older men. The causal mechanisms are unknown. Candidates include deficient feedforward (stimulation) by endogenous secretagogues and excessive feedback (inhibition) by GH or IGF-I due to age and/or relative hypoandrogenemia.
  
  
  OBJECTIVE
  Testosterone (T) supplementation in healthy older men will restrain negative feedback by systemic concentrations of IGF-I.
  
  
  METHODS
  Twenty-four healthy men (ages, 50 to 75 yr; body mass index, 24 to 30 kg/m(2)) participated in the study.
  
  
  METHODS
  We performed a prospectively randomized, double-blind, placebo-controlled assessment of the impact of pharmacological T supplementation on GH responses to randomly ordered separate-day injections of recombinant human IGF-I doses of 0, 1.0, 1.5, and 2.0 mg/m(2).
  
  
  METHODS
  Deconvolution and approximate entropy analyses of pulsatile, basal, and entropic (pattern-sensitive) modes of GH secretion were conducted.
  
  
  RESULTS
  Recombinant human IGF-I injections 1) elevated mean and peak serum IGF-I concentrations dose-dependently (both P < 0.001); 2) suppressed pulsatile GH secretion (P = 0.003), burst mass (P = 0.025), burst number (P = 0.005), interpulse variability (P = 0.032), and basal GH secretion (P = 0.009); and 3) increased secretory pattern regularity (P = 0.020). T administration did not alter experimentally controlled IGF-I concentrations, but it elevated mean GH concentrations (P = 0.015) and stimulated pulsatile GH secretion (frequency P = 0.037, mass per burst P = 0.038). Compared with placebo, T attenuated exogenous IGF-I's inhibition of GH secretory-burst mass (P < 0.038) without restoring pulse number, basal secretion, or pattern regularity.
  
  
  CONCLUSIONS
  The capability of systemic T to mute IGF-I feedback on pulsatile GH secretion suggests a novel mechanism for augmenting GH production.
authors.affiliation: Department of Medicine, Endocrine Research Unit, Mayo School of Graduate Medical Education, Clinical Translational Science 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: Joy N
authors.initials: JN
authors.lastname: Bailey
authors.forename: Adenborduin
authors.initials: A
authors.lastname: Adeniji
authors.forename: John M
authors.initials: JM
authors.lastname: Miles
authors.forename: Remberto
authors.initials: R
authors.lastname: Paulo
authors.forename: Mihaela
authors.initials: M
authors.lastname: Cosma
authors.forename: Cacia
authors.initials: C
authors.lastname: Soares-Welch
mesh_terms: D000368:Aged; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D025461:Feedback, Physiological; D019382:Human Growth Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012044:Regression Analysis; D013739:Testosterone / Q000494:pharmacology*
chemical_list: D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I