Gonadal status and body mass index jointly determine growth hormone (GH)-releasing hormone/GH-releasing peptide synergy in healthy men

J Clin Endocrinol Metab. 2008 Mar;93(3):944-50. doi: 10.1210/jc.2007-1388. Epub 2007 Dec 11.

Abstract

Context: Sex steroid hormones potentiate whereas increased body mass index (BMI) represses GH secretion. Whether sex steroids modify the negative effect of BMI on secretagogue-induced GH secretion in men is not known. The issue is important in designing GH-stimulation regimens that are relatively insensitive to both gonadal status and adiposity.

Objective: Our objective was to compare the relationships between BMI and peptide-stimulated GH secretion in men with normal and reduced testosterone and estradiol availability.

Setting: The study was performed at an academic medical center.

Subjects: Healthy young men were included in the study.

Interventions: Randomized separate-day iv infusion of saline and/or maximally effective doses of L-arginine/GHRH, L-arginine/GH-releasing peptide (GHRP)-2, and GHRH/GHRP-2 in eugonadal (n=12) and experimentally hypogonadal (n=10) men was performed.

Outcomes: Regression of paired secretagogue-induced GH responses on BMI was determined.

Results: In eugonadal men, peak GH concentrations correlated negatively with BMI. In particular, BMI accounted for only 38% of the response variability after L-arginine/GHRH (P=0.0165), but 62% after GHRH/GHRP-2 (P=0.0012) and 65% after L-arginine/GHRP-2 (P=0.00075). In contrast, in hypogonadal men, GH responses were uncorrelated with BMI. The negative effects of BMI on peak GH responses in eugonadal and hypogonadal states differed most markedly after stimulation with GHRH/GHRP-2 (P=0.0019). This contrast was corroborated using integrated GH responses (P=0.0007).

Conclusions: Short-term experimental gonadal sex hormone depletion attenuates dual secretagogue-stimulated GH secretion in lean young men. The inhibitory effect of relative adiposity on GH secretion appears to predominate over that of acute sex steroid withdrawal.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Arginine / pharmacology
  • Body Mass Index*
  • Drug Synergism
  • Growth Hormone-Releasing Hormone / pharmacology*
  • Human Growth Hormone / metabolism*
  • Humans
  • Hypogonadism / metabolism*
  • Male
  • Oligopeptides / pharmacology*

Substances

  • Oligopeptides
  • Human Growth Hormone
  • Growth Hormone-Releasing Hormone
  • Arginine
  • growth hormone-releasing peptide-2