Astrocytes and brain function: Implications for reproduction

Recent evidence suggests that astrocytes have important neuroregulatory functions in addition to their classic functions of support and segregation of neurons. These newly revealed functions include regulation of neuron communication, neurosecretion, and synaptic plasticity. Although these actions occur throughout the brain, this review will focus on astrocyteneuron interactions in the hypothalamus, particularly with respect to their potential contribution to the regulation of gonadotropin-releasing hormone (GnRH) secretion and reproduction. Hypothalamic astrocytes have been documented to release a variety of neuroactive factors, including transforming growth factors-α and -β, insulin-like growth factor-1, prostaglandin E2, and the neurosteroid, 3α-hydroxy-5α-pregnane-20-one. Each of these factors has been shown to stimulate GnRH release, and receptors for each factor have been documented on GnRH neurons. Astrocytes have also been implicated in the regulation of synaptic plasticity in key areas of the hypothalamus that control GnRH release, an effect achieved by extension and retraction of glial processes (i.e., glial ensheathment). Through this mechanism, the number of synapses on GnRH neurons and GnRH regulatory neurons can potentially be modulated, thereby influencing the activation state of GnRH neurons. The steroid hormone 17β-estradiol, which triggers the GnRH and luteinizing hormone surge, has been shown to induce the astrocyte-regulated changes in hypothalamic synaptic plasticity, as well as enhance formation and release of the astrocyte neuroactive factors, thereby providing another potential mechanistic layer for astrocyte regulation of GnRH release. As a whole, these studies provide new insights into the diversity of astrocytes and their potential role in reproductive neuroendocrine function.