Neonatal Lipopolysaccharide Exposure Exacerbates Stress-Induced Suppression of Luteinizing Hormone Pulse Frequency in Adulthood

• Published in: Endocrinology (Philadelphia) 2007-12, Vol.148 (12), p.5984-5990
• Main Authors: Li, X. F, Kinsey-Jones, J. S, Knox, A. M. I, Wu, X. Q, Tahsinsoy, D, Brain, S. D, Lightman, S. L, O’Byrne, K. T
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Adults; Animals; Animals, Newborn; Biological and medical sciences; Corticotropin-releasing hormone; Endotoxins; Exposure; Female; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Gonadotropin-releasing hormone; Gonadotropin-Releasing Hormone - blood; Gonadotropin-Releasing Hormone - metabolism; Immunology; Lipopolysaccharides; Lipopolysaccharides - pharmacology; Luteinizing hormone; Luteinizing Hormone - blood; Luteinizing Hormone - metabolism; mRNA; Neonates; Ovariectomy; Pituitary; Pregnancy; Preoptic area; Preoptic area (medial); Preoptic Area - drug effects; Preoptic Area - metabolism; Pulse generators; Radioimmunoassay; Rats; Receptor mechanisms; Receptors; Receptors, Corticotropin-Releasing Hormone - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sex hormones; Time Factors; Vertebrates: endocrinology
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/en.2007-0710

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 μg/kg, ip). At 12 wk of age, they were ovariectomized and implanted with sc 17β-estradiol capsules and iv cannulas. Blood samples (25 μl) were collected every 5 min for 5 h for LH measurement. After 2 h of sampling, rats were given LPS (25 μg/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.