Neonatal lipopolysaccharide exposure exacerbates stress-induced suppression of luteinizing hormone pulse frequency in adulthood

X F Li, J S Kinsey-Jones, A M I Knox, X Q Wu, D Tahsinsoy, S D Brain, S L Lightman, K T O'Byrne

Research output: Contribution to journalArticle (Academic Journal)peer-review

37 Citations (Scopus)


Early life exposure to immunological challenge has programming effects on the adult hypothalamo-pituitary-adrenocortical axis stress responsivity, and stress is known to suppress GnRH pulse generator activity, especially LH pulses. We investigated the effects of neonatal exposure to endotoxin on stress-induced suppression of pulsatile LH secretion and the involvement of corticotropin-releasing factor (CRF) receptor mechanisms in adult rats. Pups at 3 and 5 d of age were administered lipopolysaccharide (LPS, 50 microg/kg, ip). At 12 wk of age, they were ovariectomized and implanted with sc 17beta-estradiol capsules and i.v. cannulas. Blood samples (25 microl) were collected every 5 min for 5 h for LH measurement. After 2 h of sampling, rats were given LPS (25 microg/kg, iv). CRF and CRF-R1 and CRF-R2 receptor mRNA was determined by RT-PCR in medial preoptic area (mPOA) micropunches collected at 3 h after LPS administration. There was no difference in basal LH pulse frequency between neonatal LPS- and neonatal saline-treated controls. However, neonatal endotoxin-treated rats exhibited a significantly greater LPS stress-induced suppression of LH pulse frequency. Basal mPOA CRF-R1 expression was unchanged in neonatal LPS- and neonatal saline-treated rats. However, CRF-R1 expression was significantly increased in response to LPS stress in neonatal LPS-treated animals but not in neonatal saline-treated controls. CRF and CRF-R2 expression was unchanged in all treatment groups. These data demonstrate that exposure to bacterial endotoxin in early neonatal life programs long-term sensitization of the GnRH pulse generator to the inhibitory influence of stress in adulthood, an effect that might involve up-regulation of CRF-R1 expression in the mPOA.

Original languageEnglish
Pages (from-to)5984-90
Number of pages7
Issue number12
Publication statusPublished - Dec 2007


  • Animals
  • Animals, Newborn
  • Female
  • Gene Expression/drug effects
  • Gonadotropin-Releasing Hormone/blood
  • Lipopolysaccharides/pharmacology
  • Luteinizing Hormone/blood
  • Pregnancy
  • Preoptic Area/drug effects
  • RNA, Messenger/genetics
  • Radioimmunoassay
  • Rats
  • Receptors, Corticotropin-Releasing Hormone/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors


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