Effects of chronic stress on hypothalamic lnterleukin-1 beta, interleukin-2, and gonadotrophin-releasing hormone gene expression in ovariectomized rats

The influence of chronic stress on the expression of interleukin (IL)-1 bet a and IL-2 mRNAs in ovariectomized rat brains, and the physiological conseq uences of the expression of these cytokines on hypothalamic-pituitary-gonad al (HPG) activity were investigated. Using polymerase chain reaction (PCR)- assisted semiquantitative analysis, we demonstrated alterated expression of IL-1 beta and IL-2 mRNA during repeated cold stress; the expression of bot h IL-beta and IL-2 mRNA increased in the medial preoptic area and ventromed ial hypothalamus, and decreased in the lateral hypothalamic area. In the ar cuate nucleus/median eminence, IL-2 mRNA expression was dramatically decrea sed, in contrast to the increase in IL-1 beta mRNA expression. Concomitant analysis of GnRH mRNA expression indicated significant suppression of GnRH synthesis in the chronic phase, and a strong negative correlation with cyto kine expression in the medial preoptic area. Similar results were obtained in intact females exposed to this stress. These results, together with prev ious pharmacological studies, suggest that chronic stress may induce reprod uctive dysfunction through the effects of stress-induced expression of endo genous cytokines.