title: Estimation of the size and shape of GH secretory bursts in healthy women using a physiological estradiol clamp and variable-waveform deconvolution model.
abstract: Because estrogen production and age are strong covariates, distinguishing their individual impact on hypothalamo-pituitary regulation of growth hormone (GH) output is difficult. In addition, at fixed elimination kinetics, systemic GH concentration patterns are controlled by three major signal types [GH-releasing hormone (GHRH), GH-releasing peptide (GHRP, ghrelin), and somatostatin (SS)] and by four dynamic mechanisms [the number, mass (size), and shape (waveform) of secretory bursts and basal (time invariant) GH secretion]. The present study introduces an investigative strategy comprising 1) imposition of an experimental estradiol clamp in pre- (PRE) and postmenopausal (POST) women; 2) stimulation of fasting GH secretion by each of GHRH, GHRP-2 (a ghrelin analog), and l-arginine (to putatively limit SSergic restraint); and 3) implementation of a flexible-waveform deconvolution model to estimate basal GH secretion simultaneously with the size and shape of secretory bursts, conditional on pulse number. The combined approach unveiled the following salient percent POST/PRE contrasts: 1) only 27% as much GH secreted in bursts during fasting (P < 0.001); 2) markedly attenuated burstlike GH secretion in response to bolus GHRP-2 (29%), bolus GHRH (30%), l-arginine (37%), constant GHRP-2 (38%), and constant GHRH (42%) (age contrasts, 0.0016 </= P </= 0.027); and 3) a 160% prolongation and 32% abbreviation of the time required to achieve maximal GH secretion after injection of l-arginine and bolus GHRP-2, respectively (both, P < 0.001). Accordingly, age selectively determines both the size (amount) and shape (waveform) of GH secretory bursts in healthy women independently of the short-term estrogen milieu.
authors.affiliation: Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. veldhuis.johannes@mayo.edu
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Keenan
authors.forename: Cyril Y
authors.initials: CY
authors.lastname: Bowers
mesh_terms: D000368:Aged; D000465:Algorithms; D001120:Arginine / Q000494:pharmacology; D004311:Double-Blind Method; D004958:Estradiol / Q000097:blood; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006728:Hormones / Q000097:blood; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D015233:Models, Statistical; D009842:Oligopeptides / Q000494:pharmacology; D011446:Prospective Studies
chemical_list: D006728:Hormones; D009842:Oligopeptides; D019382:Human Growth Hormone; D004958:Estradiol; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; C091874:growth hormone-releasing peptide-2