Hypothalamic injury causes female sexual precocity by activating luteinizing hormone-releasing hormone (LHRH) neurons, which control sexual development. Transforming growth factor-a OCF-a) has been implicated in this process, but its involvement in normal sexual maturation is unknown. The present study addresses this issue. TGF-a mRNA and protein were found mostly in astroglia, in regions of the hypothalamus concerned with LHRH control. Hypothalamic TGF-a mRNA levels increased at times when secretion of pituitary gonadotropins-an LHRHdependent event-was elevated, particularly at the time of puberty. Conadal steroids involved in the control of LHRH secretion increased TGF-a mRNA levels. Blockade of TCF-a action in the median eminence, a site of glial-LHRH nerve terminal association, delayed puberty. These results suggest that TCF-a of glial origin is a component of the developmental program by which the brain controls mammalian sexual maturation.