Review Function-related structural plasticity of the GnRH system A role for neuronal–glial–endothelial interactions Vincent Prevot a,b,c, * , Naresh K. Hanchate a,b,c , Nicole Bellefontaine a,b,c , Ariane Sharif a,b,c , Jyoti Parkash a,b,c , Cecilia Estrella a,b,c , Cécile Allet a,b,c , Sandrine de Seranno a,b,c , Céline Campagne a,b,c , Xavier d’Anglemont de Tassigny a,b,c , Marc Baroncini a,b,c,d a Inserm, Jean-Pierre Aubert Research Center, U837, Development and Plasticity of the Postnatal Brain, F-59000 Lille, France b Univ. Nord de France, F-59000 Lille, France c UDSL, Laboratory of Anatomy, School of Medicine, Place de Verdun, F-59000 Lille, France d CHRU Lille, Department of Neurosurgery, Hôpital Roger Salengro, F-59000 Lille, France article info Article history: Available online 9 June 2010 Keywords: GnRH Astrocytes Tanycytes Endothelial cells Nitric oxide Prostaglandins Ovarian cycle Gonadal steroids Hypothalamus Reproduction abstract As the final common pathway for the central control of gonadotropin secretion, GnRH neurons are sub- jected 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 sys- tem 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 coordi- nated 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 main- tain the reproductive axis. Ó 2010 Elsevier Inc. All rights reserved. 1. 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 challeng- ing in this regard. Numerous regulatory homeostatic and external factors converge on GnRH neurons to control gonadotropin secre- tion and thereby achieve levels of fertility appropriate to the organism. Current models of neuronal plasticity stress the impor- tance 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 phys- ical 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-neurohy- pophysial 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. 2. The GnRH system GnRH is the master regulator of sexual maturation and repro- duction 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 portal blood ves- sels for delivery to the anterior pituitary. At the adenohypophysis, GnRH elicits the secretion of the gonadotropins LH and FSH, which stimulate gametogenesis and gonadal steroid secretion and thus support reproductive physiology (Fig. 1). Because GnRH neurons are the final common target for the cen- tral control of reproduction, their activity is regulated by a complex 0091-3022/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.yfrne.2010.05.003 * Corresponding author at: Inserm U837, Bâtiment Biserte, Place de Verdun, 59045 Lille Cedex, France. Fax: +33 320 53 85 62. E-mail address: vincent.prevot@inserm.fr (V. Prevot). Frontiers in Neuroendocrinology 31 (2010) 241–258 Contents lists available at ScienceDirect Frontiers in Neuroendocrinology journal homepage: www.elsevier.com/locate/yfrne