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 assume that ghrelin can: (a) stimulate pituitary GH secretion directly; (b) antagonize inhibition of pituitary GH release by SRIF; (c) oppose suppression of GHRH neurons in the arcuate nucleus (ArC) by SRIF; and (d) 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: (i) constant GHS infusion stimulates pulsatile GH secretion; (ii) GHS and GHRH synergize in vivo;(iii) 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 trough; (iv) transgenetic silencing of the neuronal GHS receptor blunts GH pulses in the female; and (v) 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.