title: Arthritis-susceptible Lewis rats fail to emerge from the stress hyporesponsive period.
abstract: Susceptibility to streptococcal cell wall (SCW)-induced arthritis in 4- to 6-week-old Lewis (LEW/N) rats is associated with blunted glucocorticoid production secondary to a profound defect in inflammatory mediator-induced hypothalamic corticotropin-releasing hormone (CRH) biosynthesis and secretion. The relative SCW arthritis resistance in histocompatible Fischer (F344/N) rats, on the other hand, is associated with robust hypothalamic-pituitary-adrenal (HPA) axis responses to inflammatory mediators. In this study, we investigated HPA axis responses to SCW during the postnatal developmental period in LEW/N and F344/N rats. We found that SCW-induced plasma corticosterone (CORT) responses do not significantly increase during development in LEW/N, while such responses clearly appear at postnatal day 14 in F344/N and outbred Harlan-Sprague-Dawley (HSD) rats. Additionally, LEW/N rats fail to exhibit the normal ontogenic increase in CRH mRNA levels in the paraventricular nucleus (PVN), whereas their SCW-induced PVN CRH mRNA responses are blunted compared to F344/N at postnatal day 14. Taken together, these results suggest that LEW/N rats fail to emerge completely from their stress hyporesponsive period. This may account for the lack of stress responsiveness in young adult LEW/N rats, and consequently, for their susceptibility to SCW-induced arthritis and other inflammatory diseases.
authors.affiliation: Arthritis and Rheumatism Branch, NIAMS, Bethesda, MD 20892.
authors.forename: S
authors.initials: S
authors.lastname: Aksentijevich
authors.forename: H J
authors.initials: HJ
authors.lastname: Whitfield
authors.forename: W S
authors.initials: WS
authors.lastname: Young
authors.forename: R L
authors.initials: RL
authors.lastname: Wilder
authors.forename: G P
authors.initials: GP
authors.lastname: Chrousos
authors.forename: P W
authors.initials: PW
authors.lastname: Gold
authors.forename: E M
authors.initials: EM
authors.lastname: Sternberg
mesh_terms: D000818:Animals; D001168:Arthritis / Q000503:physiopathology*; D002473:Cell Wall / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D009693:Nucleic Acid Hybridization; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013297:Streptococcus pyogenes / Q000502:physiology; D013312:Stress, Physiological / Q000503:physiopathology*
chemical_list: D012333:RNA, Messenger; D003346:Corticotropin-Releasing Hormone