Glial-neuronal interactions in the neuroendocrine control of mammalian puberty: Facilitatory effects of gonadal steroids

It is now clear that astroglial cells actively contribute to both the gener ation and how of information within the central nervous system, In the hypo thalamus, astrocytes regulate the secretory activity of neuroendocrine neur ons, A small subset of these neurons secrete luteinizing hormone-releasing hormone (LHRH), a neuropeptide essential for sexual development and adult r eproductive function, Astrocytes stimulate LHRH secretion via cell-cell sig naling mechanisms involving growth factors recognized by receptors with eit her serine/threonine or tyrosine kinase activity. Two members of the epider mal growth factor (EGF) family and their respective tyrosine kinase recepto rs appear to play key roles in this regulatory process. Transforming growth factor-alpha (TGF alpha) and its distant congeners, the neuregulins (NRGs) , are produced in hypothalamic astrocytes, They stimulate LHRH secretion in directly, via activation of erbB-1/erbB-2 and erbB-4/erbB-2 receptor comple xes also located on astrocytes, Activation of these receptors leads to rele ase of prostaglandin E-2 (PGE(2)), which then binds to specific receptors o n LHRH neurons to elicit LHRH secretion. Gonadal steroids facilitate this g lia-to-neuron communication process by acting at three different steps alon g the signaling pathway, They (a) increase astrocytic gene expression of at least one of the EGF-related ligands (TGF alpha), (b) increase expression of at least two of the receptors (erbB-4 and erbB-2), and (c) enhance the L HRH response to PGE(2) by up-regulating in LHRH neurons the expression of s pecific PGE(2) receptor isoforms. Focal overexpression of TGF alpha in eith er the median eminence or preoptic area of the hypothalamus accelerates pub erty, Conversely, blockade of either TGF alpha or NRG hypothalamic actions delays the process. Thus, both TGF alpha and NRGs appear to be physiologica l components of the central neuroendocrine mechanism controlling the initia tion of female puberty. By facilitating growth factor signaling pathways in the hypothalamus, ovarian steroids accelerate the pace and progression of the pubertal process. (C) 1999 John Wiley & Sons, Inc.