Secretagogues govern GH secretory-burst waveform and mass in healthy eugonadal and short-term hypogonadal men

Johannes D. Veldhuis, Daniel M. Keenan

Research output: Contribution to journalArticle

4 Scopus citations

Abstract

Background: GH pulses are putatively initiated by hypothalamic GH-releasing hormone (GHRH), amplified by GH-releasing peptide (GHRP), and inhibited by somatostatin (SS). Objective: To ascertain how secretagogues control the waveform (time evolution of release rates) as well as the mass of secretory bursts. Design: We quantified the shape of GH secretory bursts evoked by continuous combined i.v. infusion of maximally effective doses of GHRH and GHRP-2, and by bolus injection of each peptide after delivering L-arginine to restrain hypothalamic SS release in 12 healthy young men. Methods: A mathematically verified and experimentally validated variable-waveform deconvolution model was applied to intensively sampled GH time series. Results: The secretory-burst mode (time from burst onset to maximal secretion) was 19 ± 0.6 9 min during saline infusion, and fell to a) 10.4±3.Omin during constant dual stimulation with GHRH/GHRP-2 (P<0.01), b) 14.6±1.8min after L-arginine/GHRH (P<0.025), and c) 15.0± 1.0 min after L-arginine/GHRH (P<0.01). Secretagogues augmented the mass of GH secreted in pulses by 44-, 42-, and 16-fold respectively, over saline (2.2±0.81 μg/l per h; P<0.001 for each). Pulse number and variability were unaffected. Applying the same methodology to ten other young men with acute leuprolide-induced hypogonadism yielded comparable waveform and mass estimates. Conclusion: The present analyses in men demonstrate that peptidyl secretagogues modulate not only the magnitude but also the time course of the GH-release process in vivo independently of the short-term sex-steroid milieu.

Original languageEnglish (US)
Pages (from-to)547-554
Number of pages8
JournalEuropean journal of endocrinology
Volume159
Issue number5
DOIs
StatePublished - Nov 1 2008

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ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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