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This Article Accepted manuscript (PDF) All Versions of this Article: EJE-08-0414v1 159/5/547    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Veldhuis, J. Articles by Keenan, D. PubMed PubMed Citation Articles by Veldhuis, J. Articles by Keenan, D.

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

J Veldhuis, Endocrine Research Unit, Mayo Clinic, Rochester, 55905, United States
D Keenan, Statistics, University of Virginia, Charlottesville, United States

Correspondence: Johannes Veldhuis, Email: veldhuis.johannes{at}mayo.edu

Abstract

Growth-hormone (GH) pulses are putatively initiated by hypothalamic GH-releasing hormone (GHRH), amplified by GH-releasing peptide (GHRP) and inhibited by somatostatin (SS). Whether these 3 peptides control the waveform (time-evolution of release rates) as well as the mass of secretory bursts is not known. To address this question, 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. A mathematically verified and experimentally validated variable-waveform deconvolution model was applied to intensively sampled GH time series (Am J Physiol 285: R664-R673, 2003) The secretory-burst mode (time from burst onset to maximal secretion) was 19 ± 0.69 min during saline infusion, and fell to (a) 10.4 ± 3.0 min during constant dual stimulation with GHRH/GHRP-2 (P < 0.01), (b) 14.6 ± 1.8 min 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-fold, 42-fold and 16-fold, respectively, over saline (2.2 ± 0.81 ug/L/hr) [P < 0.001 for each]. Pulse number and variability were unaffected. Applying the same methodology to 10 other young men with leuprolide-induced hypogonadism yielded comparable waveform and mass estimates. In 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.