The transforming growth factor alpha gene family is involved in the neuroendocrine control of mammalian puberty

Abstract

The concept is proposed that the central control of mammalian female puberty requires the interactive participation of neuronal networks and glial cells of the astrocytic lineage. According to this concept neurons and astrocytes control the pubertal process by regulating the secretory activity of those neurons that secrete luteinizing hormone-releasing hormone (LHRH). LHRH, in turn, governs sexual development by stimulating the secretion of pituitary gonadotropins. Astrocytes affect LHRH neuronal function via a cell–cell signaling mechanism involving several growth factors and their corresponding receptors. Our laboratory has identified two members of the epidermal growth factor/transforming growth factor (EGF/TGFα) family as components of the glial-neuronal interactive process that regulates LHRH secretion. Transforming growth factor alpha (TGFα) and its distant congener neu-differentiation factor, NDF, are produced in hypothalamic astrocytes and stimulate LHRH release via a glial intermediacy. The actions of TGFα and NDF on hypothalamic astrocytes involve the interactive activation of their cognate receptors and the synergistic effect of both ligands in stimulating the glial release of prostaglandin E₂ (PGE₂). In turn, PGE₂ acts directly on LHRH neurons to stimulate LHRH release. A variety of experimental approaches has led to the conclusion that both TGFα and NDF are physiological components of the central mechanism controlling the initiation of female puberty.