Department of Anatomy, School of Medicine, University of Athens, 75 Mikras Asias Str., 11527 Goudi, Athens, Greece.
Pituitary. 2013 Jun;16(2):275-86. doi: 10.1007/s11102-012-0417-5.
Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.
甲状腺功能亢进症与皮质醇增多症有关，尽管主要负责皮质醇增多症的基因座仍不清楚。本研究的目的是评估甲状腺功能亢进症对下丘脑-垂体-肾上腺（HPA）轴功能完整性的影响，确定HPA 轴中主要受影响的基因座，并解决甲状腺状态改变的时间依赖性影响。在接受安慰剂或甲状腺素（50μg）药理剂量治疗 7 或 60 天的假甲状腺切除术雄性 Sprague-Dawley 大鼠和甲状腺切除术大鼠中，体外和原位检查了 HPA 轴的每个组成部分的功能完整性。短期和长期甲状腺功能亢进大鼠的基础血浆皮质酮和皮质酮结合球蛋白（CBG）浓度显着升高，60 天后也升高。基础血浆 ACTH 水平与对照组相似。长期甲状腺功能亢进大鼠下丘脑 CRH 含量和 KCL-和精氨酸血管加压素（AVP）诱导的下丘脑培养物中 CRH 释放的幅度均增加。短期和长期甲状腺功能亢进动物的前垂体中 ACTH 和β-内啡肽的含量均显着增加。短期甲状腺功能亢进大鼠的前垂体中 POMC mRNA 表达的基础水平显着增加，而慢性甲状腺功能亢进动物显示应激诱导的 POMC mRNA 表达增加。取自短期甲状腺功能亢进大鼠的肾上腺培养物对外源性 ACTH 的反应是皮质酮反应过度，而取自 60 天甲状腺功能亢进动物的肾上腺培养物的反应与对照相似。这些发现表明甲状腺功能亢进症与皮质醇增多症和 HPA 轴功能障碍有关，随着甲状腺功能亢进症持续时间的增加，这种功能障碍变得更加明显。证据表明，实验性甲状腺功能亢进症与 HPA 轴的中枢活性增强有关。
