Pulsatile secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus is crucial for the neuroendocrine regulation of pituitary function in the hypothalamic- pituitary-gonadal axis. The origin and molecular nature of GnRH pulsatility are, however, still unknown. In the present study, we simulated the ultradian rhythmicity by in silico modeling approach. Based on the recent study in which pulsatile secretion of GnRH is originated from transcriptional oscillation, a negative feedback-based self-oscillation model at the levels of GnRH mRNA and GnRH secretion was formulated. Furthermore, this model was expanded to examine the network effect with 100 synaptically interconnected neurons. This model exhibits ultradian rhythmicity and synchronization effect as com-pared to the randomly firing network model. This in silico approach appears to be valuable in elucidating the molecular nature and origin of biorhythmicity in the complex GnRH neuronal apparatus.

Keywords: Hypothalamus, GnRH, pulsatility, neural network model, negative feedback, gene expression-secretion coupling, oscillation