Transforming growth factor-alpha gene expression in the hypothalamus is developmentally regulated and linked to sexual maturation.
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.
Ma
Y J
YJ
Division of Neuroscience, Oregon Regional Primate Research Center, Beaverton 97006.
Junier
M P
MP
Costa
M E
ME
Ojeda
S R
SR
D000818:Animals; D016375:Antisense Elements (Genetics); D002396:Catechols / Q000008:administration & dosage / Q000494:pharmacology; D004343:Drug Implants; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D008473:Median Eminence / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology; D010052:Ovariectomy; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012741:Sexual Maturation / Q000502:physiology*; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D020032:Tyrphostins
D016375:Antisense Elements (Genetics); D002396:Catechols; D004343:Drug Implants; D009570:Nitriles; D012333:RNA, Messenger; D016211:Transforming Growth Factor alpha; D020032:Tyrphostins; C060152:tyrphostin 47; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases