Endogenous glucocorticoids in autoimmune disease and in the thymus / Applicant: Oskar Lechner

• VerfasserIn: Lechner, Oskar
• Place / Publishing House: 1997
• Year of Publication: 1997
• Language: English
• Physical Description: VIII, 138 Bl.; Ill., graph. Darst.
• Notes: Zsfassung in dt. Sprache

eng: In the first part of the present thesis, we focused on the possible underlying mechanisms of the disturbed immuno-neuroendocrine communication via the hypothalamo-pituitary-adrenal axis in murine lupus. Establishing the circadian rhythms of corticosterone, DHEA-S, ACTH, and melatonin, we found: i) In AID-prone mice, the circadian melatonin rhythm seems to be uncoupled from the light/dark cycle and to directly influence adrenal corticosterone production, resulting in elevated plasma corticosterone levels during the resting phase. ii) We could confirm the existence of a disturbed immuno-neuroendocrine communication in (NZB/W) F1, NZB and NZW. iii) A clear correlation of pathology parameters for autoimmunity and the altered immuno-modulatory response to cytokine application could be found. iv) The tested murine strains show higher baseline corticosterone levels, and reach the same corticosterone levels after application of GIF compared to normal strains. In the second part of my thesis, I asked if the whole GC synthetic pathway might perhaps take place in primary lymphoid tissues of mice and chickens, hopefully forming the basis for later investigations in murine and avian models of different AID. Using modified thin layer chromatography as well as RIA we were able to show: v) The presence of the whole set of steroidogenic enzymes, necessary for GC production in the murine and chicken thymus, as well as the chicken bursa. vi) Preliminary data indicate that intrathymic steroid production follows a different circadian pattern than adrenal synthesis, at least in healthy SWISS and lupus-prone MRL/MP-fas"l"p"r mice. vii) Thymic epithelial cells are the steroidogenic cells within the thymus. viii) An intact thymic architecture seems to be necessary for GC synthesis.