Neonatal exposure to lipopolysacharride (LPS) programs long-term changes in hypothalamo-pituitary-adrenocotical (HPA) axis activity, resulting in an increased sensitivity to stress (1). Neonatal LPS (nLPS) exposure also causes long-term sensitisation of the hypothalamo-pituitary-gonadal (HPG) axis to the inhibitory influences of stress in adulthood (2). Further, we have shown that nLPS results in delayed puberty and a concomitant decrease in kisspeptin (Kiss1) mRNA expression within the medial preoptic area (mPOA) in the female rat. Whilst the mechanisms underlying the actions of nLPS on pubertal development remain unknown, it is possible that the stress neuropeptide, corticotrophin-releasing factor (CRF), may play a role. The aim of the present study is to examine the role of CRF in both nLPS delayed puberty and normal pubertal development. All surgical procedures were undertaken using ketamine (100 mg/kg i.p) and Rompun (10 mg/kg i.p.) anaesthesia. Sprague-Dawley pups received either LPS (50μg/kg, i.p.) or saline (0.05ml) on post natal day 3 and 5 (2), or had no neonatal treatments. At postnatal day 28, rats were implanted with intracerebroventricular (icv) cannulae connected to an osmotic mini-pump. The neonatal saline (nSAL) or nLPS treated rats received either a CRF receptor antagonist astressin (AST, 4nmol/day) or artificial cerebrospinal fluid (aCSF) (n=4-7 per group). The neonatal none-treated rats were distributed between four experimental groups; no surgery control, aCSF (0.5μl/day), 0.2nmol/day or 0.4 nmol/day CRF (n=3-7 per group). Compounds were infused for 2 weeks; rats were then monitored for vaginal opening and first oestrus as markers of puberty. An additional group of neonatal none-treated rats were infused with either aCSF (0.5μl/day), CRF (0.4nmol/day) or AST (4nmol/day) (n=6-8) and seven days following icv implantation (post natal day 35) were decapitated and brains removed and stored at −80 C. QPCR was used to determine Kiss1 and its receptor (Kiss1r) mRNA levels in brain punches of the mPOA and arcuate nucleus (ARC). nLPS exposure resulted in a delay in both the day of vaginal opening (nLPS-aCSF; 38±0.18 vs nSAL-aCSF; 36.71±0.2; Mean±SEM; P<0.05) and first oestrus (nLPS-aCSF; 38.71±0.26: nSAL-aCSF; 36.71±0.21; Mean±SEM; P<0.05). The CRF antagonist was unable to reverse the nLPS-induced delay in puberty, but advanced puberty in nSAL treated rats (nSAL-AST; 34.75±0.23; P<0.05). CRF resulted in a delay in puberty onset (P<0.05) and decreased Kiss1 mRNA expression in the mPOA, but not in the ARC. Kiss1r expression remained unchanged. These data suggests that nLPS-induced pubertal delay is not mediated by CRF. However, under normal conditions an inhibitory CRF tone is evident since a CRF antagonist advanced puberty and CRF per se delayed puberty and decreased mPOA Kiss1 expression.