Veldhuis JD, Keenan DM, Bowers CY. Estimation of the size and shape of GH secretory bursts in healthy women using a physiological estradiol clamp and variable-waveform deconvolution model. Am J Physiol Regul Integr Comp Physiol 293: R1013-R1021, 2007. First published May 30, 2007; doi:10.1152/ajpregu.00159.2007.-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 Ͻ 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 Յ P Յ 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 Ͻ 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 GROWTH HORMONE (GH) and sex-steroid concentrations decline together in aged mammals (26,40). Although estrogen is a prominent positive determinant of GH secretion in humans, whether reduced GH output in aging is due to relative estrogen deficiency is difficult to parse for several reasons. First, GH secretion is correlated negatively with age and positively with estrogen availability, whereas age is related inversely to estrogen concentrations (38). Second, GH secretion is controlled via multiple peptidyl pathways that are both stimulatory and inhibitory (26,33,40). Finally, the dynamic mechanisms that govern plasma GH concentrations include, for any given distribution volume and elimination kinetics, both pulsatile (burstlike) and basal (time invariant) secretion (40).Whereas the regulation of basal (Ͻ10% of total) GH secretion has not been well studied, pulsatile hormone release is controlled by three maj...