Secretagogues govern GH secretory-burst waveform and mass in healthy eugonadal and short-term hypogonadal men.
نویسندگان
چکیده
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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ورودعنوان ژورنال:
- European journal of endocrinology
دوره 159 5 شماره
صفحات -
تاریخ انتشار 2008