It has been earlier proposed that oxytocin could play a facilitatory role in the preovulatory luteinizing hormone (LH) surge both in rats and humans. We here provide evidence that oxytocin also facilitates sexual maturation in female rats. The administration of an oxytocin antagonist for six days to immature female rats decreased gonadotropin-releasing hormone (GnRH) pulse frequency ex vivo, and delayed the age at vaginal opening and first estrus. The in vitro reduction in GnRH pulse frequency required chronic blockade of oxytocin receptors, as it was not acutely observed after a single injection of the antagonist. Hypothalamic explants exposed to the antagonist in vitro, showed a reduced GnRH pulse frequency and failed to respond to oxytocin with GnRH release. Prostaglandin E₂ (PGE₂) mimicked the stimulatory effect of oxytocin on GnRH pulse frequency, and inhibition of PG synthesis blocked the effect of oxytocin, suggesting that oxytocin accelerates pulsatile GnRH release via PGE₂. The source of PGE₂ appears to be astrocytes, because oxytocin stimulates PGE₂ release from cultured hypothalamic astrocytes. Moreover, astrocytes express oxytocin receptors whereas GnRH neurons do not. These results suggest that oxytocin facilitates female sexual development, and that this effect is mediated by a mechanism involving glial production of PGE₂.