Abstract
Over the past four decades it has become clear that prostaglandin E2 (PGE2), a phospholipid-derived signaling molecule, plays a fundamental role in modulating the gonadotropin-releasing hormone (GnRH) neuroendocrine system and in shaping the hypothalamus. In this review, after a brief historical overview, we highlight studies revealing that PGE2 released by glial cells such as astrocytes and tanycytes is intimately involved in the active control of GnRH neuronal activity and neurosecretion. Recent evidence suggests that hypothalamic astrocytes surrounding GnRH neuronal cell bodies may respond to neuronal activity with an activation of the erbB receptor tyrosine kinase signaling, triggering the release of PGE2 as a chemical transmitter from the glia themselves, and, in turn, leading to the feedback regulation of GnRH neuronal activity. At the GnRH neurohemal junction, in the median eminence of the hypothalamus, PGE2 is released by tanycytes in response to cell–cell signaling initiated by glial cells and vascular endothelial cells. Upon its release, PGE2 causes the retraction of the tanycyte end-feet enwrapping the GnRH nerve terminals, enabling them to approach the adjacent pericapillary space and thus likely facilitating neurohormone diffusion from these nerve terminals into the pituitary portal blood. In view of these new insights, we suggest that synaptically associated astrocytes and perijunctional tanycytes are integral modulatory elements of GnRH neuronal function at the cell soma/dendrite and nerve terminal levels, respectively.
Highlights
Sexual development, puberty, and adult fertility are achieved by events that are initiated within the central nervous system and require the maturation and function of a neural network that transmits both homeostatic and external cues to the discrete hypothalamic neuronal population that releases gonadotropinreleasing hormone (GnRH) from neuroendocrine terminals within the median eminence into the pituitary portal vessels to control gonadotropins secretion (Terasawa and Fernandez, 2001; Herbison and Neill, 2006; Malpaux, 2006; Ojeda and Skinner, 2006; Plant, 2006; Donato et al, 2011)
Using patchclamp recordings in brain slices from transgenic mice expressing green fluorescent protein (GFP) under the control of the GnRH promoter, we showed that prostaglandin E2 (PGE2) induced a reversible membrane depolarization of GnRH neurons leading to the initiation of spike firing via the postsynaptic effect involving activation of a non-selective cation current (Figure 5; Clasadonte et al, 2011) reminiscent of the ones recently described in GnRH neurons by other groups (Zhang et al, 2008; Roland and Moenter, 2011)
Several observations made over the last two decades have demonstrated that PGE2 known for almost 40 years to play an important role in the regulation of the hypothalamic–pituitary–gonadal axis, is a transmitter released by astrocytes and tanycytes, and intimately linked with GnRH neuronal function in both the preoptic region and the median eminence of the hypothalamus, where the cell bodies and the neuroendocrine terminals of GnRH neurons in rodents are respectively located
Summary
Puberty, and adult fertility are achieved by events that are initiated within the central nervous system and require the maturation and function of a neural network that transmits both homeostatic and external cues to the discrete hypothalamic neuronal population that releases gonadotropinreleasing hormone (GnRH) from neuroendocrine terminals within the median eminence into the pituitary portal vessels to control gonadotropins (luteinizing hormone, LH and follicle stimulating hormone, FSH) secretion (Terasawa and Fernandez, 2001; Herbison and Neill, 2006; Malpaux, 2006; Ojeda and Skinner, 2006; Plant, 2006; Donato et al, 2011) These gonadotropins act on the ovaries and testis to regulate the secretion of sex steroids and the production of eggs and sperm. Astrocytes and tanycytes likely play a fundamental role in shaping and regulating the GnRH system
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