Abstract
Hypothalamic injury causes female sexual precocity by activating luteinizing hormone-releasing hormone (LHRH) neurons, which control sexual development. Transforming growth factor-alpha (TGF-alpha) has been implicated in this process, but its involvement in normal sexual maturation is unknown. The present study addresses this issue. TGF-alpha mRNA and protein were found mostly in astroglia, in regions of the hypothalamus concerned with LHRH control. Hypothalamic TGF-alpha mRNA levels increased at times when secretion of pituitary gonadotropins--an LHRH-dependent event--was elevated, particularly at the time of puberty. Gonadal steroids involved in the control of LHRH secretion increased TGF-alpha mRNA levels. Blockade of TGF-alpha action in the median eminence, a site of glial-LHRH nerve terminal association, delayed puberty. These results suggest that TGF-alpha of glial origin is a component of the developmental program by which the brain controls mammalian sexual maturation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antisense Elements (Genetics)
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Catechols / administration & dosage
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Catechols / pharmacology
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Drug Implants
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ErbB Receptors / antagonists & inhibitors
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Estradiol / pharmacology
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Female
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Gene Expression
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Gonadotropin-Releasing Hormone / metabolism*
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Hypothalamus / drug effects
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Hypothalamus / growth & development
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Hypothalamus / physiology*
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Median Eminence / drug effects
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Median Eminence / growth & development
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Median Eminence / physiology
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Nitriles / administration & dosage
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Nitriles / pharmacology
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Ovariectomy
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Protein-Tyrosine Kinases / antagonists & inhibitors
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RNA, Messenger / metabolism*
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Rats
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Rats, Sprague-Dawley
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Sexual Maturation / physiology*
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Transforming Growth Factor alpha / genetics*
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Tyrphostins*
Substances
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Antisense Elements (Genetics)
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Catechols
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Drug Implants
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Nitriles
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RNA, Messenger
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Transforming Growth Factor alpha
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Tyrphostins
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tyrphostin 47
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Gonadotropin-Releasing Hormone
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Estradiol
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ErbB Receptors
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Protein-Tyrosine Kinases