A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System

Vidal, Alexandre; Clément, Frédérique

doi:10.1111/j.1365-2826.2010.02055.x

Cited by 21 publications

(19 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Then, the signal generated by variable y displays an alternation of surge, small oscillations and surge phases as illustrated in Figure 1. We refer to [26] for an expanded explanation of the model behavior based on this approach.…”

Section: Constraints On the Secretor Parameters And Statement Of The mentioning

confidence: 99%

See 1 more Smart Citation

Mixed-Mode Oscillations in a Multiple Time Scale Phantom Bursting System

Krupa¹,

Vidal²,

Desroches³

et al. 2012

SIAM J. Appl. Dyn. Syst.

View full text Add to dashboard Cite

In this work we study mixed mode oscillations in a model of secretion of GnRH (Gonadotropin Releasing Hormone). The model is a phantom burster consisting of two feedforward coupled FitzHugh-Nagumo systems, with three time scales. The forcing system (Regulator) evolves on the slowest scale and acts by moving the slow null-cline of the forced system (Secretor). There are three modes of dynamics: pulsatility (transient relaxation oscillation), surge (quasi steady state) and small oscillations related to the passage of the slow null-cline through a fold point of the fast null-cline. We derive a variety of reductions, taking advantage of the mentioned features of the system. We obtain two results; one on the local dynamics near the fold in the parameter regime corresponding to the presence of small oscillations and the other on the global dynamics, more specifically on the existence of an attracting limit cycle. Our local result is a rigorous characterization of small canards and sectors of rotation in the case of folded node with an additional time scale, a feature allowing for a clear geometric argument. The global result gives the existence of an attracting unique limit cycle, which, in some parameter regimes, remains attracting and unique even during passages through a canard explosion.

show abstract

Section: Constraints On the Secretor Parameters And Statement Of The mentioning

confidence: 99%

“…System (1) has been proposed in [5,6,26] to model the dynamics of GnRH secretion by hypothalamic neurons in female mammals. Subsystem (1a)-(1b), called the Secretor, represents the mean-field approximation of the GnRH neuron population dynamics.…”

Section: Introductionmentioning

confidence: 99%

Mixed-Mode Oscillations in a Multiple Time Scale Phantom Bursting System

Krupa¹,

Vidal²,

Desroches³

et al. 2012

SIAM J. Appl. Dyn. Syst.

View full text Add to dashboard Cite

show abstract

“…Making the electrical subsystem excitable rather than oscillatory is critical for allowing that model to reproduce the experimentally observed bursts, which have very long silent phases. Another recent model for GnRH neurons also involves FTM [60]. …”

Section: Discussionmentioning

confidence: 99%

Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?

Watts

Fendler

Merrins

et al. 2014

SIAM J. Appl. Dyn. Syst.

View full text Add to dashboard Cite

Pancreatic islets exhibit bursting oscillations in response to elevated blood glucose. These oscillations are accompanied by oscillations in the free cytosolic Ca2+ concentration (Cac), which drives pulses of insulin secretion. Both islet Ca2+ and metabolism oscillate, but there is some debate about their interrelationship. Recent experimental data show that metabolic oscillations in some cases persist after the addition of diazoxide (Dz), which opens K(ATP) channels, hyperpolarizing β-cells and preventing Ca2+ entry and Ca2+ oscillations. Further, in some islets in which metabolic oscillations were eliminated with Dz, increasing the cytosolic Ca2+ concentration by the addition of KCl could restart the metabolic oscillations. Here we address why metabolic oscillations persist in some islets but not others, and why raising Cac restarts oscillations in some islets but not others. We answer these questions using the dual oscillator model (DOM) for pancreatic islets. The DOM can reproduce the experimental data and shows that the model supports two different mechanisms for slow metabolic oscillations, one that requires calcium oscillations and one that does not.

show abstract

“…In contrast, timescale separation was at the source of the design and analysis of a multiple timescale model involving coupled FHN systems and coping not only with GnRH pulses, but also with the recurrent alternation between the pulse and surge regimes [37]. This GnRH pulse and surge generator is also able to capture the modulation of pulse frequency along an ovarian cycle and the effects of estradiol or progesterone bolus [46], in agreement with the whole corpus of biological knowledge drawn from GnRH portal blood data.…”

Section: 2) Computational Approaches Of the Gnrh And Lh Pulse Genermentioning

confidence: 99%

Advances in computational modeling approaches of pituitary gonadotropin signaling

Yvinec

Crépieux

Reiter

et al. 2018

Expert Opinion on Drug Discovery

View full text Add to dashboard Cite

Pituitary gonadotropins play an essential and pivotal role in the control of human and animal reproduction within the hypothalamic-pituitary-gonadal (HPG) axis. The computational modeling of pituitary gonadotropin signaling encompasses phenomena of different natures such as the dynamic encoding of gonadotropin secretion, and the intracellular cascades triggered by gonadotropin binding to their cognate receptors, resulting in a variety of biological outcomes. Areas covered: The authors provide an overview of the historical and ongoing issues in modeling and data analysis related to gonadotropin secretion in the field of both physiology and neuroendocrinology. They mention the different mathematical formalisms involved, their interest and limits. They also discuss open statistical questions in signal analysis associated with key endocrine issues and review recent advances in the modeling of the intracellular pathways activated by gonadotropins, which yields promising development for innovative approaches in drug discovery. Expert opinion: The greatest challenge to be tackled in computational modeling of pituitary gonadotropin signaling is the embedding of gonadotropin signaling within its natural multi-scale environment, from the single cell level, to the organic and whole HPG level. The development of modeling approaches of G protein-coupled receptor signaling, together with multicellular systems biology may lead to unexampled mechanistic understanding with critical expected fallouts in the therapeutic management of reproduction.

show abstract

A Dynamical Model for the Control of the Gonadotrophin‐Releasing Hormone Neurosecretory System

Cited by 21 publications

References 46 publications

Mixed-Mode Oscillations in a Multiple Time Scale Phantom Bursting System

Mixed-Mode Oscillations in a Multiple Time Scale Phantom Bursting System

Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?

Advances in computational modeling approaches of pituitary gonadotropin signaling

Contact Info

Product

Resources

About