NDLI: Targeting transforming growth factor alpha expression to discrete loci of the neuroendocrine brain induces female sexual precocity.

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Targeting transforming growth factor alpha expression to discrete loci of the neuroendocrine brain induces female sexual precocity.

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Targeting transforming growth factor alpha expression to discrete loci of the neuroendocrine brain induces female sexual precocity.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mccann, S. M. Breakefield, X. O. Coffey, R. J. Hill, D. F. Sena-esteves, M. Costa, M. E. Ojeda, S. R. Rage, F.
Description	Author Affiliation: Rage F ( Division of Neuroscience, Oregon Regional Primate Research Center/Oregon Health Sciences University, Beaverton 97006, USA.);
Abstract	Precocious puberty of cerebral origin is a poorly understood disorder of human sexual development, brought about by the premature activation of those neurons that produce luteinizing hormone-releasing hormone (LHRH), the neuropeptide controlling sexual maturation. An increased production of transforming growth factor alpha (TGF alpha) in the hypothalamus has been implicated in the mechanism underlying both normal and precocious puberty. We have now used two gene delivery systems to target TGF alpha overexpression near LHRH neurons in immature female rats. Fibroblasts infected with a retroviral construct in which expression of the human TGF alpha gene is constitutively driven by the phosphoglycerate kinase promoter, or transfected with a plasmid in which TGF alpha expression is controlled by an inducible metallothionein promoter, were transplanted into several regions of the hypothalamus. When the cells were in contact with LHRH nerve terminals or in the vicinity of LHRH perikarya, sexual maturation was accelerated. These results suggest that precocious puberty of cerebral origin may result from a focal disorder of TGF alpha production within the confines of the LHRH neuron microenvironment.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	94
Language	English
Publisher	National Academy of Sciences
Publisher Date	1997-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gonadotropin-Releasing Hormone Physiology Hypothalamus Neurosecretory Systems Puberty, Precocious Physiopathology Sexual Maturation Transforming Growth Factor Alpha 3T3 Cells Transplantation Animals Gene Transfer Techniques Mice Phosphoglycerate Kinase Genetics Plasmids Promoter Regions, Genetic Rats, Sprague-Dawley Recombinant Fusion Proteins Biosynthesis Retroviridae Transfection Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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