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

Growth hormone (GH) secretion is controlled by GH-releasing hormone (GHRH), the GH release-inhibiting hormone somatostatin (SRIF), and autofeedback co nnections. The ensemble network produces sexually dimorphic patterns of GH secretion. In an effort to formalize this system, we implemented a determin istically based autonomous feedback-driven construct of five principal dose -responsive regulatory interactions: GHRH drive of GH pituitary release, co mpetitive 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 success ive 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 expli cated as arising from a reciprocal interaction between GH and GHRH during p eriods of low SRIF secretion. The applicability of this formalism to neuroe ndocrine 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 p ulse generator to achieve pulsatile GH output. Further evolution of interac tive constructs could aid in exploring more complex feedback postulates tha t confer the vivid sexual dimorphism of female GH profiles.