Novel relationships of age, visceral adiposity, insulin-like growth factor (IGF)-I and IGF binding protein concentrations to growth hormone (GH) releasing-hormone and GH releasing-peptide efficacies in men during experimental hypogonadal clamp

J Clin Endocrinol Metab. 2009 Jun;94(6):2137-43. doi: 10.1210/jc.2009-0136. Epub 2009 Apr 7.

Abstract

Background: Sex steroids influence GH secretion in complex ways.

Hypothesis: Analyses in a low sex-steroid milieu will help unveil the effects of age and other nonsteroidal regulators on GH secretion.

Context: The study was conducted in a tertiary medical center.

Subjects: The study group included 13 healthy young men and 12 healthy older men.

Methods: We used GnRH agonist-induced down-regulation of testosterone and estradiol secretion, followed by consecutive infusion of l-arginine and GHRH or GHRP-2, to test secretagogue efficacies.

Outcomes: We measured basal and pulsatile GH secretion.

Results: During experimental testosterone/estradiol deprivation, older (57 +/- 1.7 yr) men maintained: 1) 6.8-fold less pulsatile GH secretion (P < 0.001); and 2) 2-fold lower maximal GH responses to GHRH (P = 0.0065) and GHRP-2 (P = 0.022) than young (23 +/- 1.1 yr old) individuals. Stepwise forward-selection regression analyses identified: 1) abdominal visceral fat as a dominant negative predictor of both GHRH (R(2) = 0.49; P = 0.001) and GHRP-2 (R(2) = 0.38; P = 0.005) efficacies; and 2) fasting IGF-I concentration as a major positive correlate of GHRH (R(2) = 0.52; P < 0.001) and GHRP-2 (R(2) = 0.31; P = 0.018) efficacies. Unstimulated pulsatile GH secretion was jointly correlated with IGF-I and IGFBP-3 (P = 0.039).

Conclusion: Measures of body composition (abdominal visceral fat) and pulsatile GH action (IGF-I) explain up to one half of interindividual variability in the efficacies of GHRH and GHRP-2 in sex steroid-depleted men. Accordingly, normative ranges for maximal single peptide-stimulated GH secretion in short-term hypogonadal states should incorporate the influence of these determinants as well as age.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology
  • Adult
  • Aging / physiology*
  • Cohort Studies
  • Double-Blind Method
  • Growth Hormone-Releasing Hormone / pharmacology*
  • Human Growth Hormone / metabolism
  • Humans
  • Hypogonadism / blood
  • Hypogonadism / metabolism
  • Hypogonadism / pathology*
  • Insulin-Like Growth Factor Binding Proteins / blood*
  • Insulin-Like Growth Factor Binding Proteins / physiology
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / metabolism*
  • Insulin-Like Growth Factor I / physiology
  • Intra-Abdominal Fat / physiology*
  • Male
  • Middle Aged
  • Oligopeptides / pharmacology*
  • Treatment Outcome
  • Young Adult

Substances

  • Insulin-Like Growth Factor Binding Proteins
  • Oligopeptides
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Growth Hormone-Releasing Hormone
  • growth hormone-releasing peptide-2