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

Abstract

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.