title: Hypothalamic-pituitary-adrenal axis activation by experimental periodontal disease in rats.
abstract: Organisms respond to inflammatory conditions by mounting a co-ordinated complex series of adaptive responses involving the immune, nervous and endocrine systems that are aimed at restoring the homeostatic balance. We have recently shown in a rat model that inappropriate hypothalamic-pituitary-adrenal (HPA) axis regulation and a subsequent inability to mount a suitable glucocorticoid response to gingival inflammation may influence susceptibility to periodontal disease. This study was designed to investigate whether ligature- and bacterial lipopolysaccharide (LPS)-induced inflammation in the gingival connective tissues may activate this physiological axis, and to further explore the significance of HPA regulation in periodontal disease. Experimental periodontal disease was induced in major histocompatibility complex (MHC)-identical but HPA low (LEW) and high (F344) responding rat strains. We tested (1) whether ongoing periodontal disease activates the HPA axis as measured by corticosterone levels, and (2) whether genetic differences in HPA regulation modulate periodontal disease progression. In the F344 strain. the periodontal tissue destruction was more severe. This observation was associated with a significant increase of corticosterone levels in F344 rats only. Addition of LPS at the gingival inflammatory site led to a further increase of corticosterone levels and disease severity in F344 rats. These findings illustrate a positive feedback loop between the HPA axis and periodontal disease: the disease activates the HPA axis, and a genetically determined high HPA responsivity further increases disease susceptibility.
authors.affiliation: Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway. tbreivik@odont.uio.no
authors.forename: T
authors.initials: T
authors.lastname: Breivik
authors.forename: P S
authors.initials: PS
authors.lastname: Thrane
authors.forename: P
authors.initials: P
authors.lastname: Gjermo
authors.forename: P K
authors.initials: PK
authors.lastname: Opstad
authors.forename: R
authors.initials: R
authors.lastname: Pabst
authors.forename: S
authors.initials: S
authors.lastname: von Hörsten
mesh_terms: D016301:Alveolar Bone Loss / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D016009:Chi-Square Distribution; D003345:Corticosterone / Q000097:blood; D025461:Feedback, Physiological; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D008026:Ligation; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008439:Maxillary Diseases / Q000503:physiopathology; D015213:Neuroimmunomodulation; D017622:Periodontal Attachment Loss / Q000503:physiopathology; D010510:Periodontal Diseases / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew
chemical_list: D008070:Lipopolysaccharides; D003345:Corticosterone