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

Endocrine Research Unit, Clinical Translational Research Unit, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, Minnesota 55905, USA¹ Department of Statistics, University of Virginia, Charlottesville, Virginia 22904, USA

(Correspondence should be addressed to J D Veldhuis; Email: veldhuis.johannes{at}mayo.edu)

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±0.69 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-, 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.