title: The effect of hypothalamic lesions on hypothalamo-pituitary-adrenal axis activity and inflammation in adjuvant-induced arthritis.
abstract: Adjuvant-induced arthritis (AA) was induced in control and in hypothalamic lesioned Piebald-Viral-Glaxo (PVG) rats. Following discrete paraventricular nucleus (PVN) lesions plasma corticosterone was increased 14 days after adjuvant injection as in controls, when hind paw inflammation was apparent. PVN lesion did not affect the severity of inflammation.In contrast, following medial basal hypothalamus (MBH) lesions adjuvant did not increase corticosterone levels and the increase in paw volume at day 14 was potentiated. Basal proopiomelanocortin(POMC) mRNA expression in the anterior lobe was unchanged by PVN lesions and decreased by MBH lesions. AA increased POMC mRNA in controls and in both PVN and MBH lesioned rats. After complete MBH lesion, surviving anterior pituitary tissue maintained morning levels of corticosterone.Thus, AA may activate the hypothalamo-pituitary-adrenal axis without the mediation of PVN neurones projecting to the median eminence. However, the loss of the corticosterone response to AA and the increase in severity of inflammation in the MBH lesioned rats suggests a central (non-PVN) component mediates effects of inflammation. Furthermore, the increase in POMC mRNA in the MBH lesioned AA rats suggests that part of this process is not mediated by releasing factors in the hypothalamo-hypophysial portal system, and that extrahypothalamic(peripheral) mediators act on the pituitary during chronic inflammation.
authors.affiliation: Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest, Hungary. makara8 koki.hu
authors.forename: G B
authors.initials: GB
authors.lastname: Makara
authors.forename: M S
authors.initials: MS
authors.lastname: Harbuz
authors.forename: T L
authors.initials: TL
authors.lastname: Coventry
authors.forename: D S
authors.initials: DS
authors.lastname: Jessop
authors.forename: D
authors.initials: D
authors.lastname: Zelena
authors.forename: S L
authors.initials: SL
authors.lastname: Lightman
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D005620:Freund's Adjuvant; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D010913:Pituitary-Adrenal System / Q000378:metabolism* / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011333:Pro-Opiomelanocortin; D005620:Freund's Adjuvant; D003345:Corticosterone