A Model for the Pulsatile Secretion of Gonadotropin-Releasing Hormone from Synchronized Hypothalamic Neurons

Cultured gonadotropin-releasing hormone (GnRH) neurons have been shown to express GnRH receptors. GnRH binding to its receptors activates three types of G-proteins at increasing doses. These G-proteins selectively activate or inhibit GnRH secretion by regulating the intracellular levels of Ca 2+ and...

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Bibliographic Details
Published in:Biophysical journal 2006-07, Vol.91 (1), p.74-83
Main Authors: Khadra, Anmar, Li, Yue-Xian
Format: Article
Language:English
Subjects:
Animals
Autocrine Communication - physiology
Biological Clocks - physiology
Biophysical Theory and Modeling
Biophysics
Cells, Cultured
Computer Simulation
Gonadotropin-Releasing Hormone - secretion
Hormones
Humans
Hypothalamus - physiology
Mathematical models
Models, Neurological
Nerve Net - physiology
Neurons
Neurons - physiology
Proteins
Pulsatile Flow - physiology
Synaptic Transmission - physiology
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Summary:Cultured gonadotropin-releasing hormone (GnRH) neurons have been shown to express GnRH receptors. GnRH binding to its receptors activates three types of G-proteins at increasing doses. These G-proteins selectively activate or inhibit GnRH secretion by regulating the intracellular levels of Ca 2+ and cAMP. Based on these recent observations, we build a model in which GnRH plays the roles of a feedback regulator and a diffusible synchronizing agent. We show that this GnRH-regulated GnRH-release mechanism is sufficient for generating pulsatile GnRH release. The model reproduces the observed effects of some key drugs that disturb the GnRH pulse generator in specific ways. Simulations of 100 heterogeneous neurons revealed that the synchronization mediated by a common pool of diffusible GnRH is robust. The population can generate synchronized pulsatile signals even when all the individual GnRH neurons oscillate at different amplitudes and peak at different times. These results suggest that the positive and negative effects of the autocrine regulation by GnRH on GnRH neurons are sufficient and robust in generating GnRH pulses.
ISSN:0006-3495
1542-0086
DOI:10.1529/biophysj.105.080630