Marina Chugunova | Applied Math, University of Waterloo
Synchronized secretion of gonadotropin-releasing hormone (GnRH) by GnRH neurons.
A relatively small population (800-2000) of GnRH neurons is located in the hypothalamus of mammals. These neurons secrete GnRH hormone and are intrinsic oscillators with respect to GnRH secretion. The synchronized release of GnRH triggers the reproductive axis by initiating the production of the next two types of hormones in this chain.
In spite of intensive research on the functioning of GnRH neurons for the last twenty years, in many ways, the dynamic mechanisms driving the production of GnRH are still a mystery. Scattered throughout the hypothalamus, GnRH neurons are a quite challenging object for studies in vivo. On the other side, when studied in vitro, these neurons’ characteristics are affected by mechanical and chemical factors of the immortalization process.
Another challenge is the unique morphology of GnRH neurons. Recently, it was discovered that GnRH neuron projections exhibit the properties of both axons and dendrites (so, they are called “dendrons”). Dendrons of distinct GnRH neurons often “bundle” with the connexons as a connection. Moreover, it has been discovered that action potential in GnRH neurons is initiated not in the soma, but at the part of the dendrite called “iSite” with high density of sodium channels.
The secretion of GnRH in a single GnRH neuron is regulated both by autocrine regulation and external signalling. Two of many signalling agents discovered recently are kisspeptin and estradiol. Kisspeptin is secreted by the kisspeptin neurons and estradiol is transported upstream of the GnRH transportation. Kisspeptin depolarizes the membrane of the GnRH neuron acting as a stimulator of the action potential, and estradiol provides negative feedback. At the same time, several researchers reported that GnRH has the ability to secrete kisspeptin on its own. One more regulating mechanism is present due to extra- synaptic GABAA receptors. Finally, there were several reports that synchronization of only the electrical activity of GnRH cells does not synchronize the secretion of GnRH.
The goal of the upcoming research is to reveal the mechanism of the synchronization of GnRH secretion by creating a mathematical model with measurable biological parameters.