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Am J Physiol Regul Integr Comp Physiol 281: R38-R51, 2001;
0363-6119/01 $5.00
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Vol. 281, Issue 1, R38-R51, July 2001

A construct of interactive feedback control of the GH axis in the male

Leon S. Farhy1, Martin Straume1,2,5, Michael L. Johnson1,2,3, Boris Kovatchev2,4, and Johannes D. Veldhuis1,2,5

1 Department of Internal Medicine, Division of Endocrinology and Metabolism, 4 Departments of Psychiatric Medicine and Health Evaluation Sciences, 3 Department of Pharmacology, The University of Virginia Health System, 2 Center for Biomathematical Technology, and 5 National Science Foundation Center for Biological Timing, University of Virginia, Charlottesville, Virginia 22908

Growth hormone (GH) secretion is controlled by GH-releasing hormone (GHRH), the GH release-inhibiting hormone somatostatin (SRIF), and autofeedback connections. The ensemble network produces sexually dimorphic patterns of GH secretion. In an effort to formalize this system, we implemented a deterministically based autonomous feedback-driven construct of five principal dose-responsive regulatory interactions: GHRH drive of GH pituitary release, competitive inhibition of GH release by SRIF, GH autofeedback via SRIF with a time delay, delayed GH autonegative feedback on GHRH, and SRIF inhibition of GHRH secretion. This formulation engenders a malelike pattern of successive GH volleys due jointly to positive time-delayed feedback of GH on SRIF and negative feedback of SRIF on GH and GHRH. The multipeak volley is explicated as arising from a reciprocal interaction between GH and GHRH during periods of low SRIF secretion. The applicability of this formalism to neuroendocrine control is explored by initial parameter sensitivity analysis and is illustrated for selected feedback-dependent experimental paradigms. The present construct is not overparameterized and does not require an ad hoc pulse generator to achieve pulsatile GH output. Further evolution of interactive constructs could aid in exploring more complex feedback postulates that confer the vivid sexual dimorphism of female GH profiles.

growth hormone; somatostatin; growth hormone-releasing hormone; hypothalamus; mathematical model


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