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


METHODS
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.


CONCLUSIONS
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.
Veldhuis
Johannes D
JD
Endocrine Research Unit, Mayo Medical and Graduate Schools, Mayo Clinic, Rochester, Minnesota 55905, USA. veldhuis.johannes@mayo.edu
Keenan
Daniel M
DM
D000328:Adult; D004958:Estradiol / Q000097:blood / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000008:administration & dosage*; D006728:Hormones / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D007006:Hypogonadism / Q000188:drug therapy* / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism*; D007262:Infusions, Intravenous; D008297:Male; D008954:Models, Biological; D009842:Oligopeptides / Q000008:administration & dosage*; D011673:Pulsatile Flow / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage*; D013737:Testis / Q000378:metabolism; D013739:Testosterone / Q000097:blood / Q000378:metabolism
D006728:Hormones; D009842:Oligopeptides; D019382:Human Growth Hormone; D013739:Testosterone; D004958:Estradiol; D013004:Somatostatin; D013007:Growth Hormone-Releasing Hormone; C091874:growth hormone-releasing peptide-2