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/TGF␣) family as components of the glial-neuronal interactive process that regulates LHRH secretion. Transforming growth factor alpha (TGF␣) and its distant congener neu-differentiation factor, NDF, are produced in hypothalamic astrocytes and stimulate LHRH release via a glial intermediacy. The actions of TGF␣ 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 E 2 (PGE 2 ). In turn, PGE 2 acts directly on LHRH neurons to stimulate LHRH release. A variety of experimental approaches has led to the conclusion that both TGF␣ and NDF are physiological components of the central mechanism controlling the initiation of female puberty.Keywords: glial cells; hypothalamus; growth factors; sexual development; astrocytes; cell-cell communication; LHRH neuronsThe onset of mammalian female puberty requires the ronal network is well-documented, recent studies have raised the possibility that glial cells may also play a functional activation of a specialized group of hypothalamic neurons that produce luteinizing hormonerole in the control of LHRH neuronal activity. 9 Anatomical evidence demonstrates that the glial ensheathreleasing hormone (LHRH), the neurohormone governing sexual maturation and reproductive function. ment of LHRH neurons in both primates and rodents is substantial, 10,11 the main difference between species Elucidation of the mechanisms controlling LHRH neuronal function is critical for the understanding of the being a more prominent glial apposition to LHRH perikarya in primates. 10 Glial apposition of LHRH cellular and molecular processes underlying sexual development and adult reproductive capacity. It is well nerve terminals in the median eminence of the hypothalamus is, however, similarly abundant in both rats accepted that transsynaptic inputs, both excitatory 1,2 and inhibitory, 3 contribute to the central regulation of and primates. The median eminence contains astrocytes and modified ependymoglial cells known as tany-LHRH secretion. A combination of a decrease in transsynaptic inhibitory tone and an increase in excitatory cytes. 12 These specialized glial cells line the ventral portion of the third ventricle and send their processes inputs to LHRH neurons is tho...

Neonatal perturbation of neurotrophic signaling results in abnormal sensorimotor gating and social interaction in adults: implication for epidermal growth factor in cognitive development

“…52 This factor also stimulates the release of luteinizing hormone-releasing hormone and therefore is implicated in the neuroendocrine system. 53,54 In spite of such biological significance of the EGFR ligands, molecular mechanisms of their activities are poorly understood. The EGFR ligands, such as EGF and TGFa enhance monoamine functions and development.…”

Polarized endocytosis and transcytosis in the hypothalamic tanycytes of the rat

“…Interestingly, the ligands of most of these receptors have been immunocytochemically detected in hypothalamic tanycytes, viz. those of basic fibroblast growth factor (Gibson et al 2000), transforming growth factors alpha (Ojeda et al 1990(Ojeda et al , 1992(Ojeda et al , 1997 and beta (Melcangi et al 1995;Martini et al 1997) andIGF-I (García-Segura et al 1991;Dueñas et al 1994). The case of IGF-I deserves special consideration; tanycytes display IGF-I receptors (CardonaGómez et al 2000) and contain immunoreactive IGF-I (García-Segura et al 1991;Dueñas et al 1994) but no IGF-I mRNA (Fernández-Galaz et al 1997).…”

“…The functional significance of this anatomical arrangement has been the matter of much controversy (Rodríguez 1976;Akmayev and Fidelina 1981;Flament-Durand and Brion 1985;McQueen 1994;Wittkowski 1998;García-Segura et al 1999). A solid body of evidence associates β tanycytes, and β 1 tanycytes in particular, to the mechanism of release of gonadotrophin-releasing hormone (GnRH) from the terminals of the GnRH neurons to the portal blood (Hökfelt 1973;Rodríguez et al 1982;Ojeda et al1990Ojeda et al , 1992Ojeda et al , 1997King and Rubin 1994;Ma 1998, Wittkowski 1998;Prevot et al 1999Prevot et al , 2003Blázquez et al 2002).…”

The adolescent brain and age-related behavioral manifestations

“…Opinions differ as to whether this effect is mediated by kainate [161], NMDA, or dl-aamino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) [607] forms of the glutamate receptor [57], although stimulation of each receptor type has been shown to facilitate GnRH release [74,425]. Glutamate may not only stimulate GnRH release directly, but also indirectly via stimulating the release of the prostaglandin PGE 2 by local astrocytes, with this PGE 2 also facilitating GnRH release [389].…”