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  • Title: Secretagogues govern GH secretory-burst waveform and mass in healthy eugonadal and short-term hypogonadal men.
    Author: Veldhuis JD, Keenan DM.
    Journal: Eur J Endocrinol; 2008 Nov; 159(5):547-54. PubMed ID: 18703567.
    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+/-0.69 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 microg/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.
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