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This Article Full Text Full Text (PDF) All Versions of this Article: 293/3/R1013    most recent 00159.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Veldhuis, J. D. Articles by Bowers, C. Y. Search for Related Content PubMed PubMed Citation Articles by Veldhuis, J. D. Articles by Bowers, C. Y.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

Estimation of the size and shape of GH secretory bursts in healthy women using a physiological estradiol clamp and variable-waveform deconvolution model

¹Endocrine Research Unit, Mayo Medical and Graduate Schools, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota; ²Department of Statistics, University of Virginia, Charlottesville, Virginia; and ³Division of Endocrinology, Department of Internal Medicine, Tulane University Health Sciences Center, New Orleans, Louisiana

Submitted 5 March 2007 ; accepted in final form 28 May 2007

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.

somatotropin; ghrelin; growth hormone-releasing hormone; somatostatin; secretagogues; estrogen; female; human