SEX-DIFFERENCES IN THE HYPOTHALAMO-PITUITARY-ADRENAL AXIS RESPONSE TOINFLAMMATORY AND NEUROENDOCRINE STRESSORS - EVIDENCE FOR A PITUITARY DEFECT IN THE AUTOIMMUNE DISEASE-SUSCEPTIBLE FEMALE LEWIS RAT

Susceptibility to inflammatory disease in infantile Lewis (LEW/N) fema le rats seems to be related to their impaired hypothalamo-pituitary-ad renal (HPA) axis response to different inflammatory stimuli, while the relative resistance to this type of disease in Fischer (F344/N) femal e rats is apparently due to their potent HPA axis response to the same stimuli. In the present study, we attempted to elucidate whether ther e is an impairment in the HPA axis response in the juvenile female LEW /N rat to inflammatory and noninflammatory stimuli, and also to determ ine whether the endogenous sex-steroid environment influences the HPA axis function in both strains of rats. For these purposes, juvenile F3 44/N and LEW/N rats of both sexes were submitted to different treatmen ts: (a) inhalation of normal atmosphere or ether vapors for 1 min (Eth er); (b) i.p. injection of vehicle alone or containing CRH (0.5 mu g/r at), arginine vasopressin (AVP; 5 mu g/rat), angiotensin II (AII; 5 mu g/rat), insulin (INS; 0.3 IU/rat), bacterial lipopolysaccharide (LPS; 100 mu g/rat) or snake venom (SV; 100 mu g/rat). Rats were then kille d at different time intervals (in min) after treatments: 20 for Ether, AVP and CRH, 30 for AII, 45 for INS, 60 for SV and 120 for LPS. Our r esults indicate: (1) the existence of a clear sexual dimorphism in the rat HPA axis function under both basal and stress conditions, with a general hyperresponse in females compared with males to a variety of n euroendocrine stressors; in F344/N female rats, a hyperresponse to dif ferent inflammatory stimuli was also found; (2) a decreased ACTH secre tion in plasma to CRH and inflammatory stimuli (LPS and SV) in LEW/N v s. F344/N female rats, and (3) an intact hypothalamo-corticotrope resp onse to Ether, AII, INS and AVP treatments in female LEW/N rats. Our f indings demonstrate the existence of a sexual dimorphic pattern in the rat HPA axis function, under basal and stimulated conditions, and fur ther support the hypothesis that decreased corticotrope response to CR H-mediated events might be responsible for the high susceptibility of the LEW/N female rat to autoimmune disease.