Emerging evidence suggests that, in addition to neuronal inputs, growth factors of glial origin are also important in the control of mammalian puberty via a cell-cell interaction that ultimately affects the neurons that release gonadotropin-releasing hormone (GnRH), a neurohormone controlling sexual development. Among these growth factors, transforming growth factor-alpha (TGF alpha) appears to be one of the physiologic components that controls the onset of female puberty by affecting GnRH neuronal activity in a glia-mediated autocrine/paracrine manner. Specifically, TGF alpha induces glia to produce bioactive substances, such as prostaglandin E2 (PGE2). In turn, PGE2 directly acts on GnRH neurons to stimulate the release of GnRH. Furthermore, the neuroregulin of glial origin neu differentiation factor (NDF) was found to facilitate the action of TGF alpha, suggesting that other growth factors may exert their biologic effects on GnRH neuronal function via a glia/neuron interaction. Another indication that glial cells may be involved in the regulation of neuroendocrine function is the presence of estrogen receptors on hypothalamic astrocytes. Thus, region-specific glial cells appear to play an integral role in the regulation of neuroendocrine function.