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

Autor: Sergio R. Ojeda, Ying J. Ma
Rok vydání: 1999
Předmět:
Zdroj: Journal of Neurobiology. 40:528-540
ISSN: 1097-4695
0022-3034
DOI: 10.1002/(sici)1097-4695(19990915)40:4<528::aid-neu9>3.0.co;2-v
Popis: It is now clear that astroglial cells actively contribute to both the generation and flow of information within the central nervous system. In the hypothalamus, astrocytes regulate the secretory activity of neuroendocrine neurons. A small subset of these neurons secrete luteinizing hormone-releasing hormone (LHRH), a neuropeptide essential for sexual development and adult reproductive function. Astrocytes stimulate LHRH secretion via cell–cell signaling mechanisms involving growth factors recognized by receptors with either serine/threonine or tyrosine kinase activity. Two members of the epidermal growth factor (EGF) family and their respective tyrosine kinase receptors appear to play key roles in this regulatory process. Transforming growth factor-α (TGFα) and its distant congeners, the neuregulins (NRGs), are produced in hypothalamic astrocytes. They stimulate LHRH secretion indirectly, via activation of erbB-1/erbB-2 and erbB-4/erbB-2 receptor complexes also located on astrocytes. Activation of these receptors leads to release of prostaglandin E2 (PGE2), which then binds to specific receptors on LHRH neurons to elicit LHRH secretion. Gonadal steroids facilitate this glia-to-neuron communication process by acting at three different steps along the signaling pathway. They (a) increase astrocytic gene expression of at least one of the EGF-related ligands (TGFα), (b) increase expression of at least two of the receptors (erbB-4 and erbB-2), and (c) enhance the LHRH response to PGE2 by up-regulating in LHRH neurons the expression of specific PGE2 receptor isoforms. Focal overexpression of TGFα in either the median eminence or preoptic area of the hypothalamus accelerates puberty. Conversely, blockade of either TGFα or NRG hypothalamic actions delays the process. Thus, both TGFα and NRGs appear to be physiological components of the central neuroendocrine mechanism controlling the initiation of female puberty. By facilitating growth factor signaling pathways in the hypothalamus, ovarian steroids accelerate the pace and progression of the pubertal process. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 528–540, 1999
Databáze: OpenAIRE
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