Nikolopoulou Elena, Mytilinaios Dimitrios, Calogero Aldo E, Kamilaris Themis C, Troupis Theodore, Chrousos George P, Johnson Elizabeth O
Department of Anatomy, School of Medicine, University of Athens, 75 Mikras Asias Str., Goudi, 11572, Athens, Greece.
Endocrine. 2015 Aug;49(3):828-41. doi: 10.1007/s12020-015-0528-7. Epub 2015 Feb 27.
Hyperthyroidism is associated with a significant increase in circulating glucocorticoid levels and hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. The aim of this study was to examine whether the HPA axis hyperactivity observed in hyperthyroidism may be explained by a disturbed feedback inhibition of endogenous glucocorticoids through two specific intracellular receptors in the brain: the high affinity mineralocorticoid receptor (MR) and the lower affinity glucocorticoid receptor (GR). Cytosolic receptor binding and gene expression was assessed in rats with short (7 days) and long standing (60 days) eu- and hyperthyroidism. Glucocorticoid receptor number and binding affinity (Kd) in the hippocampus were measured using [(3)H2]-dexamethasone radioreceptor assay. In situ hybridization was employed to examine the effects of hyperthyroidism on the GR and MR mRNA levels in the hippocampus and the pituitary. Both short- and long-term hyperthyroid rats showed pronounced reduction in the concentration of cytosolic GR in the hippocampus, without changes in binding affinity or changes in GR expression. In contrast, GR mRNA in the pituitary increased after 7 days and decreased after 60 days of thyroxin treatment. MR mRNA was moderately affected. Hyperthyroidism is associated with significant decreases in hippocampal GR levels supporting the hypothesis that hyperactivity of the HPA axis observed in experimentally induced hyperthyroidism may be attributed, at least in part, to decreased negative feedback at the level of the hippocampus. These findings further support the notion that a central locus is principally responsible for the hyperactivity of the HPA axis observed in hyperthyroidism.
甲状腺功能亢进与循环糖皮质激素水平显著升高以及下丘脑 - 垂体 - 肾上腺（HPA）轴功能亢进有关。本研究的目的是探讨在甲状腺功能亢进中观察到的HPA轴功能亢进是否可以通过大脑中两种特定的细胞内受体对内源性糖皮质激素的反馈抑制紊乱来解释：高亲和力盐皮质激素受体（MR）和低亲和力糖皮质激素受体（GR）。在患有短期（7天）和长期（60天）正常甲状腺功能和甲状腺功能亢进的大鼠中评估细胞溶质受体结合和基因表达。使用[（3）H2] - 地塞米松放射受体测定法测量海马体中糖皮质激素受体的数量和结合亲和力（Kd）。采用原位杂交技术研究甲状腺功能亢进对海马体和垂体中GR和MR mRNA水平的影响。短期和长期甲状腺功能亢进大鼠的海马体中细胞溶质GR浓度均显著降低，而结合亲和力或GR表达无变化。相比之下，甲状腺素治疗7天后垂体中的GR mRNA增加，60天后减少。MR mRNA受到中度影响。甲状腺功能亢进与海马体GR水平显著降低有关，支持了在实验性诱导的甲状腺功能亢进中观察到的HPA轴功能亢进至少部分可归因于海马体水平负反馈减少的假设。这些发现进一步支持了这样一种观点，即中枢位点主要负责在甲状腺功能亢进中观察到的HPA轴功能亢进。
