Mathematical modeling of perifusion cell culture experiments on GnRH signaling

DOI10.1016/J.MBS.2016.03.016zbMATH Open1341.92021arXiv1606.00463OpenAlexW2964215339WikidataQ46892986 ScholiaQ46892986MaRDI QIDQ299399FDOQ299399

Authors: N. Ezgi Temamogullari, H. F. Nijhout, M. C. Reed 

Publication date: 22 June 2016

Published in: Mathematical Biosciences (Search for Journal in Brave)

Abstract: 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.

Full work available at URL: https://arxiv.org/abs/1606.00463

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zbMATH Keywords

mathematical modelGnRHLHperifusion cell culture

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Cell biology (92C37)

Cites Work

• A mathematical model of pulse-coded hormone signal responses in pituitary gonadotroph cells
• Approximate Traveling Waves in Linear Reaction-Hyperbolic Equations
• Title not available (Why is that?)
• A mathematical model for the actions of activin, inhibin, and follistatin on pituitary gonado\-trophs

Cited In (6)

• A Model of Dispersion in Perifusion Systems
• Modeling of progesterone-induced intracellular calcium signaling in human spermatozoa
• The role of enzyme compartmentalization on the regulation of steroid synthesis
• A mathematical model of adult GnRH neurons in mouse brain and its bifurcation analysis
• Mathematical modelling of prolactin-receptor interaction and the corollary for prolactin receptor gene expression in skin
• Title not available (Why is that?)

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