A role for glial cells of the neuroendocrine brain in the central control of female sexual development

Abstract

It is now well established that astrocytes are active participants of the process by which information is generated and disseminated within the central nervous system (CNS). In the hypothalamus, astrocytes and ependymoglial cells of the median eminence, known as tanycytes, regulate the secretory activity of neuroendocrine neurons. A developmental process in which they are prominently involved is the neuro endocrine control of puberty. Mammalian puberty is initiated by an increase in pulsatile release of the decapeptide gonadotropin hormone-releasing hormone (GnRH) from a specialized subset of hypothalamic neuroendocrine neurons. Although a critical determinant of this increase is a coordinated change in the activity of neuronal networks synaptically connected to GnRH neurons, glial cells contribute to the process via two related mechanisms. One requires production of growth factors acting via receptors endowed with serine-threonine kinase or tyrosine kinase activity. The other involves plastic rearrangements of glia-GnRH neuron adhesiveness. A neuron-to-glia regulatory pathway is, in turn, provided by glutamatergic neurons which facilitate astrocytic signaling mediated by erythroblastosis B (erbB) receptors. Genetic disruption of these receptors, which mediate the actions of members of the epidermal growth factor (EGF) family of trophic factors, delays female sexual development due to impaired erbB ligand-induced glial prostaglandin E 2 (PGE 2) release. The adhesiveness of glial cells to GnRH neurons appears to involve two different cell-cell communications systems, one provided by the homophilic interactions of Synaptic Cell Adhesion Molecule (SynCAM), and the other resulting from the interaction of neuronal contactin with glial Receptor-like Protein Tyrosine Phosphatase-β (RPTPβ). Because both systems are endowed with signaling capabilities, the interaction of glial cells with GnRH neurons may not only involve secreted bioactive molecules, but also the activation of cell-cell signaling mechanisms by cell-surface adhesive molecules forming different types of intercellular junctions.