  The effects of pulsatile GnRH stimulation on anterior pituitary cells are
studied using perifusion cell cultures, where constantly moving medium over the
immo- bilized cells allows intermittent GnRH delivery. The LH content of the
outgoing medium serves as a readout of the GnRH signaling pathway activation in
the cells. The challenge lies in relating the LH content of the medium leaving
the chamber to the cellular processes producing LH secretion. To investigate
this relation we developed and analyzed a mathematical model consisting of
coupled partial differential equations describing LH secretion in a perifusion
cell culture. We match the mathematical model to three different data sets and
give cellular mechanisms that explain the data. Our model illustrates the
importance of the negative feedback in the signaling pathway and receptor
desensitization. We demonstrate that different LH outcomes in oxytocin and GnRH
stimulations might originate from different receptor dynamics and
concentration. We ana- lyze the model to understand the influence of
parameters, like the velocity of the medium flow or the fraction collection
time, on the LH outcomes. We show that slow velocities lead to high LH
outcomes. Also, we show that fraction collection times, which do not divide the
GnRH pulse period evenly, lead to irregularities in the data. We examine the
influence of the rate of binding and dissociation of GnRH on the GnRH movement
down the chamber. Our model serves as an important tool that can help in the
design of perifusion experiments and the interpretation of results.
