Review
Function-related structural plasticity of the GnRH system: A role for neuronal–glial–endothelial interactions

https://doi.org/10.1016/j.yfrne.2010.05.003Get rights and content

Abstract

As the final common pathway for the central control of gonadotropin secretion, GnRH neurons are subjected to numerous regulatory homeostatic and external factors to achieve levels of fertility appropriate to the organism. The GnRH system thus provides an excellent model in which to investigate the complex relationships between neurosecretion, morphological plasticity and the expression of a physiological function. Throughout the reproductive cycle beginning from postnatal sexual development and the onset of puberty to reproductive senescence, and even within the ovarian cycle itself, all levels of the GnRH system undergo morphological plasticity. This structural plasticity within the GnRH system appears crucial to the timely control of reproductive competence within the individual, and as such must have coordinated actions of multiple signals secreted from glial cells, endothelial cells, and GnRH neurons. Thus, the GnRH system must be viewed as a complete neuro-glial–vascular unit that works in concert to maintain the reproductive axis.

Introduction

The hypothalamus is a brain structure useful for the study of hormone- and activity-dependent plasticity. Research into the GnRH system appears to be particularly fascinating and challenging in this regard. Numerous regulatory homeostatic and external factors converge on GnRH neurons to control gonadotropin secretion and thereby achieve levels of fertility appropriate to the organism. Current models of neuronal plasticity stress the importance of transient electrical and biochemical events associated with the excitation process [44], [135]. However there is increasing evidence that activation is accompanied by other important physical phenomena. Over the past three decades, it has indeed become clear that fluctuating physiological conditions have the power to reversibly alter the structural relationships between neuronal and non-neuronal cell types, as well as the functional pathways over which information is transmitted. Function-related plasticity was first discovered in the magnocellular hypothalamo-neurohypophysial system; the activation or inactivation of this system and its downstream physiological consequences is associated with microstuctural changes [77], [232]. In this review, we will consider these aspects of the neuroendocrine control of GnRH release and the cell–cell communication processes involved in their regulation.

Section snippets

The GnRH system

GnRH is the master regulator of sexual maturation and reproduction in vertebrate [81], [158], [171], [229]. In rodents, the cell bodies of GnRH neurons are diffusely distributed in the forebrain and are particularly abundant in the preoptic region; in primates, including humans, they are also present in the tuberal region of the hypothalamus. The neuroendocrine fraction of GnRH neurons sends axons to the median eminence of the hypothalamus, where they release the neurohormone into the pituitary

Morphological plasticity

At all levels – somatic, dendritic and median eminence terminal zone – the GnRH neuroendocrine system displays an increasingly recognized degree of structural plasticity that is correlated with changes in the animal’s physiological state and, thus, with the altered functional properties of the system. Whereas plasticity at the GnRH cell body appears to result from dendritic and synaptic contact remodeling likely to require astrocyte intermediacy, plasticity in the terminal field involves

Underlying cellular mechanisms and signaling pathways

It is becoming increasingly clear from the wealth of new observations accumulated over the past decade that information processing and brain plasticity are not exclusive properties of neurons but that they are shared by astrocytes [7], [8], [13], [78], [128], [169], [232], [242]. Neuron–astrocyte interactions are thus central to the development and function of the central nervous system. Brain astrocytes also interact morphologically and functionally with vascular endothelial cells, other major

Concluding remarks

The evidence reviewed in this article demonstrates the vital role of astrocytes, tanycytes and vascular endothelial cells in cellular mechanisms that regulate function-related structural plasticity of the GnRH system. As such, their roles need to be integrated into current models of the central control of reproduction, in which neurons are not the sole contributors to the neuroendocrine release of GnRH. Rather, neurons, astrocytes and vascular endothelial cells are components of a basic unit of

Acknowledgments

This research was supported by the Institut National de la Santé et de la Recherche Médicale (Inserm, France) Grant U837, the Fondation pour la Recherche Médicale (Equipe FRM), l’Agence Nationale de la Recherche (ANR), the Indo-French Centre for the Promotion of Advanced Research (IFCPAR), the Université Lille 2 and the imaging Core of IFR114. JP, AS, and CE were postdoctoral fellows supported by IFCPAR, FRM and Inserm, respectively. NKH was supported by a fellowship from ANR. XdAdT and CC were

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