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This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/R1649    most recent 00451.2004v1 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 HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Farhy, L. S. Articles by Veldhuis, J. D. Search for Related Content PubMed PubMed Citation Articles by Farhy, L. S. Articles by Veldhuis, J. D.

APPETITE, OBESITY, DIGESTION, AND METABOLISM

Deterministic construct of amplifying actions of ghrelin on pulsatile growth hormone secretion

¹Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia; and ²Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota

Submitted 8 July 2004 ; accepted in final form 9 February 2005

Ghrelin is a native ligand for the growth hormone secretagogue (GHS) receptor that stimulates pulsatile GH secretion markedly. At present, no formal construct exists to unify ensemble effects of ghrelin, GH-releasing hormone (GHRH), somatostatin (SRIF), and GH feedback. To model such interactions, we have assumed that ghrelin can stimulate pituitary GH secretion directly, antagonize inhibition of pituitary GH release by SRIF, oppose suppression of GHRH neurons in the arcuate nucleus (ArC) by SRIF, and induce GHRH secretion from ArC. The dynamics of such connectivity yield self-renewable GH pulse patterns mirroring those in the adult male and female rat and explicate the following key experimental observations. 1) Constant GHS infusion stimulates pulsatile GH secretion. 2) GHS and GHRH display synergy in vivo. 3) A systemic pulse of GHS stimulates GH secretion in the female rat at any time and in the male more during a spontaneous peak than during a trough. 4) Transgenetic silencing of the neuronal GHS receptor blunts GH pulses in the female. 5) Intracerebroventricular administration of GHS induces GH secretion. The minimal construct of GHS-GHRH-SRIF-GH interactions should aid in integrating physiological data, testing regulatory hypotheses, and forecasting innovative experiments.

somatotropic axis; growth hormone secretagogues; feedback; mathematical model; hormone pulsatility; hypothalamus; pituitary

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				L. S. Farhy, C. Y. Bowers, and J. D. Veldhuis Model-projected mechanistic bases for sex differences in growth hormone regulation in humans Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1577 - R1593. [Abstract] [Full Text] [PDF]