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

Growth hormone (GH) pulsatility requires periventricular-nuclear somatostatin (SRIF_PeV), 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 SRIF _PeV 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 SRIF_PeV secretion after a long time latency, 2) SRIF_PeV inhibits both pituitary GH and ArC GHRH release, 3) ArC GHRH and SRIF _ArC oscillate reciprocally with brief time delay, and 4) SRIF _PeV represses and disinhibits the putative GHRH-SRIF_ArC oscillator. According to the present analytic construction, time-delayed feedforward and feedback signaling among SRIF_PeV, ArC GHRH, and SRIF_ArC could endow the complex physiological patterns of GH secretion in the male and female.