Gonadotrophin‐Releasing Hormone Nerve Terminals, Tanycytes and Neurohaemal Junction Remodelling in the Adult Median Eminence: Functional Consequences for Reproduction and Dynamic Role of Vascular Endothelial Cells

Abstract

Although coordinated actions of several areas within the hypothalamus are involved in the secretion of gonadotrophin‐releasing hormone (GnRH), the median eminence of the hypothalamus, where the nerve terminals are located, plays a particularly critical role in the release of GnRH. In adult females, prior to the preovulatory surge of GnRH, the retraction of specialised ependymoglial cells lining the floor of the third ventricle named tanycytes allows for the juxtaposition of GnRH nerve terminals with the adjacent pericapillary space of the pituitary portal vasculature, thus forming direct neurohaemal junctions. These morphological changes occur within a few hours and are reversible. Such remodelling may promote physiological conditions to enhance the central release of GnRH and potentiate oestrogen‐activated GnRH release. This plasticity involves dynamic cell interactions that bring into play tanycytes, astrocytes, vascular endothelial cells and GnRH neurones themselves. The underlying signalling pathways responsible for these structural changes are comprised of highly diffusible gaseous molecules, such as endothelial nitric oxide, and paracrine communication processes involving receptors of the erbB tyrosine kinase family, transforming growth factor beta 1 and eicosanoids, such as prostagladin E2. Some of these molecules, as a result of their ability to diffuse within the median eminence, may also serve as synchronising cues allowing for the occurrence of functionally meaningful episodes of GnRH secretion by coordinating GnRH release from the GnRH neuroendocrine terminals.

Nitric Oxide as Key Mediator of Neuron-to-Neuron and Endothelia-to-Glia Communication Involved in the Neuroendocrine Control of Reproduction

“…As the final common pathway for the central control of reproduction, gonadotropin-releasing hormone (GnRH) neurons are regulated by multiple neuronal networks and interactions with non-neuronal cells that intermingle in a complex array of transsynaptic inputs [1,2,3] and paracrine communication [4,5], subjected to the modulatory influence of gonadal steroids that prompts both chemical [6,7] and structural plasticity [8,9]. In rodents, the cell bodies of GnRH neuroendocrine neurons are mostly located in the preoptic region.…”

α-Tanycytes of the adult hypothalamic third ventricle include distinct populations of FGF-responsive neural progenitors

“…Hypothalamic tanycytes resemble embryonic radial glia, with a cell body at the ventricular zone and a long basally extending process, their morphology well-suited to their postulated role as modulators of neuroendocrine activity and homeostasis (reviewed in [13][14][15][16] ). Within the hypothalamus, tanycyte cell bodies are strictly localised to the central and posterior hypothalamus (level of the median eminence and premammillary nucleus, respectively).…”

Stem Cells in Neuroendocrinology

“…Factors that mediate these sex-dependent differences in hypothalamic neurogenesis have not yet been identified but could involve numerous levels of regulation, such as hormone-dependent plasticity (de Seranno et al 2010), differences in blood-barrier access between the sexes (Hoxha et al 2013), and hormonespecific induction of feeding behavior (Sieck et al 1978). Lastly, it is possible that it is the survival of newborn neurons, rather than (or in addition to) their proliferation, that is sexually dimorphic, as has been previously demonstrated for prenatally generated hypothalamic neurons (Waters and Simerly 2009;Forger et al 2004;Tobet and Hanna 1997;Park et al 1998).…”

“…Hypothalamic neuro-hormones collect here into a bed of fenestred capillaries belonging to the hypohyseal portal system, which then transport them to the pituitary. Within the ME, special glial cells, the tanycytes, regulate neurohormone secretion at the axon termini levels (Prevot et al 2010). These also integrate peripheral information by, for example, sensing glucose concentration and responding to thyroid hormone (Bolborea and Dale 2013;Ebling 2015).…”