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Am J Physiol Regul Integr Comp Physiol 286: R1030-R1042, 2004. First published February 26, 2004; doi:10.1152/ajpregu.00473.2003
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COMPLEX FUNCTION OF THE CENTRAL NERVOUS SYSTEM, SLEEP AND LOCOMOTION

Putative GH pulse renewal: periventricular somatostatinergic control of an arcuate-nuclear somatostatin and GH-releasing hormone oscillator

Leon S. Farhy1 and Johannes D. Veldhuis2

1Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, University of Virginia, Charlottesville, Virginia 22908; and 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Medical and Graduate Schools, General Clinical Research Center, Mayo Clinic, Rochester, Minnesota 55905

Submitted 20 August 2003 ; accepted in final form 19 February 2004

Growth hormone (GH) pulsatility requires periventricular-nuclear somatostatin(SRIFPeV), arcuate-nuclear (ArC) GH-releasing hormone (GHRH), and systemic GH autofeedback. However, no current formalism interlinks these regulatory loci in a manner that generates self-renewable GH dynamics. The latter must include in the adult rat 1) infrequent volleys of high-amplitude GH peaks in the male, 2) frequent discrete low-amplitude GH pulses in the female, 3) disruption of the male pattern by severing SRIFPeV outflow to ArC, 4) stimulation of GHRH and GH secretion by central nervous system delivery of SRIF, 5) inhibition of GH release by central exposure to GHRH, and 6) a reboundlike burst of GHRH secretion induced by stopping peripheral infusion of SRIF. The present study validates by computer-assisted simulations a simplified ensemble formulation that predicts each of the foregoing six outcomes, wherein 1) blood-borne GH stimulates SRIFPeV secretion after a long time latency, 2) SRIFPeV inhibits both pituitary GH and ArC GHRH release, 3) ArC GHRH and SRIFArC oscillate reciprocally with brief time delay, and 4) SRIFPeV represses and disinhibits the putative GHRH-SRIFArC oscillator. According to the present analytic construction, time-delayed feedforward and feedback signaling among SRIFPeV, ArC GHRH, and SRIFArC could endow the complex physiological patterns of GH secretion in the male and female.

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


Address for reprint requests and other correspondence: J. D. Veldhuis, Division of Endocrinology and Metabolism, Dept. of Internal Medicine, Mayo Medical and Graduate Schools, General Clinical Research Center, Mayo Clinic, Rochester, MN 55905 (E-mail: veldhuis.johannes{at}mayo.edu).




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