Interleukin-1-induced long-lasting changes in hypothalamic corticotropin-releasing hormone (CRH)--neurons and hyperresponsiveness of the hypothalamus-pituitary-adrenal axis.
Hypothalamic CRH neurons that control ACTH secretion from the pituitary gland have secretory terminals in the external zone of the median eminence (ZEME). These neurons can coproduce vasopressin (AVP), a neuropeptide that potentiates the ACTH releasing effects of CRH. Recently, we found increased AVP production in adult rats weeks after single exposure to a stressor, which may play a role in event-induced stress disorders. Here, we describe the long-term changes in the HPA axis of adult male rats following a single exposure to a stressor, the cytokine interleukin-1 beta (IL-1 beta). The effects on storage and release of AVP and CRH were established by quantitative immunocytochemistry, the effects on ACTH and corticosterone responses by radioimmunoassay. Single administration of IL-1 beta (5 micrograms/kg i.p.) induces a delayed (at least 4 d) and a long-lasting (at least 3 weeks) increase of vasopressin (AVP) stores in CRH terminals of the ZEME without affecting the CRH stores, and a marked increase of the fraction of CRH terminals that costore AVP. Eleven days after IL-1 beta administration, a second IL-1 beta challenge causes a marked depletion of the AVP stores in the ZEME within 2 hr, which is not seen in rats treated with vehicle 11 d earlier. This is accompanied by twofold higher ACTH and corticosterone responses, as compared to those in vehicle pretreated rats. IL-1 beta-pretreated rats also showed increased ACTH and corticosterone responses to electric footshocks. We conclude that transient activation of the HPA axis by a single administration of IL-1 beta induces a delayed and long-lasting hyperproduction, hyperstorage, and hypersecretion of AVP from hypothalamic CRH neurons that results in hyperresponsiveness of the HPA axis to subsequent stimuli.
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000502:physiology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D008473:Median Eminence / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D010913:Pituitary-Adrenal System / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D007375:Interleukin-1; D001127:Arginine Vasopressin; D003346:Corticotropin-Releasing Hormone