Fässler R, Dietrich H, Krömer G, Schwarz S, Brezinschek H P, Wick G
Institute for General and Experimental Pathology, University of Innsbruck, School of Medicine, Austria.
J Steroid Biochem. 1988;30(1-6):375-9. doi: 10.1016/0022-4731(88)90126-4.
Obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis (SAT) display several signs of a general immune dysbalance, some of which may be related to altered endocrine mechanisms such as the glucocorticoid tonus. The latter is the combined result of corticosterone (CN) production, metabolism as well as excretion, and the binding of CN to corticosteroid binding globulin (CBG) and glucocorticoid receptors (GR). The present study deals with the comparative investigation of these parameters in OS and normal White Leghorn (NWL) chickens. The results obtained with radioimmunoassay for CN and radioligand saturation assays for plasma CBG as well as GR in the thymus were as follows: (1) both OS and NWL have equal total CN levels; (2) however, OS chickens exhibit elevated CBG levels, whereas the physicochemical parameters (equilibrium affinity, specificity spectrum) of CBG were equal in OS and NWL; (3) the GR capacities and affinities were equal in both OS and NWL throughout development until thymic involution. Similarly, the specificity, affinity, and sedimentation behaviour were equal in OS and NWL. (4) Furthermore, no differences were found in the response of OS and NWL splenocytes to the suppressive effect of glucocorticoids in vitro, also excluding postreceptor alterations at the cellular level in the OS. From these findings we conclude that the increased CBG levels, which are not compensated for by either increased CN plasma levels or by increased receptor capacities or affinities in lymphatic organs, represent a diminished glucocorticoid tonus in OS chickens. This may have immunoregulatory consequences which, in turn, may contribute to the development of SAT.
患有自发性自身免疫性甲状腺炎(SAT)的肥胖品系(OS)鸡表现出一些全身免疫失衡的迹象,其中一些可能与内分泌机制改变有关,如糖皮质激素张力。后者是皮质酮(CN)产生、代谢以及排泄,以及CN与皮质类固醇结合球蛋白(CBG)和糖皮质激素受体(GR)结合的综合结果。本研究对OS鸡和正常白来航(NWL)鸡的这些参数进行了比较研究。用放射免疫分析法检测CN以及用放射配体饱和分析法检测胸腺中的血浆CBG和GR,结果如下:(1)OS鸡和NWL鸡的总CN水平相等;(2)然而,OS鸡的CBG水平升高,而CBG的物理化学参数(平衡亲和力、特异性谱)在OS鸡和NWL鸡中是相等的;(3)在整个发育过程直至胸腺退化,OS鸡和NWL鸡的GR容量和亲和力相等。同样,OS鸡和NWL鸡的特异性、亲和力和沉降行为也相等。(4)此外,在体外,OS鸡和NWL鸡脾细胞对糖皮质激素抑制作用的反应没有差异,这也排除了OS鸡细胞水平上受体后改变的可能性。从这些发现中我们得出结论,CBG水平升高,而血浆CN水平升高或淋巴器官中受体容量或亲和力增加均无法补偿这一升高,这表明OS鸡的糖皮质激素张力降低。这可能会产生免疫调节后果,进而可能导致SAT的发展。