THE TRANSFORMING-GROWTH-FACTOR ALPHA-GENE FAMILY IS INVOLVED IN THE NEUROENDOCRINE CONTROL OF MAMMALIAN PUBERTY

The concept is proposed that the central control of mammalian female p uberty requires the interactive participation of neuronal networks and glial cells of the astrocytic lineage. According to this concept neur ons and astrocytes control the pubertal process by regulating the secr etory activity of those neurons that secrete luteinizing hormone-relea sing hormone (LHRH) LHRH, in turn, governs sexual development by stimu lating the secretion of pituitary gonadotrophins. Astrocytes affect LH RH neuronal function via a cell-cell signaling mechanism involving sev eral growth factors and their corresponding receptors. Our laboratory has identified two members of the epidermal growth factor transforming growth factor (EGF/TGF-alpha) family as components of the glial-neuro nal interactive process that regulates LHRH secretion. Transforming gr owth factor alpha (TGF-alpha) and its distant congener neu-differentia tion factor, NDF, are produced in hypothalamic astrocytes and stimulat e LHRH release via a glial intermediacy. The actions of TGF-alpha and NDF on hypothalamic astrocytes involve the interactive activation of t heir cognate receptors and the synergistic effect of both ligands in s timulating the glial release of prostaglandin E-2 (PGE(2)). In turn, P GE(2) acts directly on LHRH neurons to stimulate LHRH release. A varie ty of experimental approaches has led to the conclusion that both TGF- alpha and NDF are physiological components of the central mechanism co ntrolling the initiation of female puberty.