Changes in Thyroid Status During Perinatal Development of MCT8-Deficient Male Mice
Changes in Thyroid Status During Perinatal Development of MCT8-Deficient Male Mice
复制标题
DOI：
10.1210/en.2012-2031
复制
发表时间：
2013-07-01
期刊：
影响因子：
4.8
通讯作者：
Refetoff, Samuel
中科院分区：
文献类型：
--
作者：
Ferrara, Alfonso Massimiliano;Liao, Xiao-Hui;Refetoff, Samuel
单羧酸转运蛋白 8 (MCT8) 缺乏综合征患者表现为严重的精神运动迟缓和血清甲状腺激素 (TH) 水平异常，包括高 T-3 和低 T-4 和 rT(3)。 Mct8缺陷的小鼠复制了MCT8基因突变患者的甲状腺表型。我们分析了 Mct8 缺陷小鼠围产期的血清 TH 水平以及大脑皮层和肝脏的活动，以评估 Mct8 缺陷的甲状腺异常如何发展并研究特定组织的甲状腺状态。在围产期，Mct8缺陷小鼠的甲状腺表型与成年小鼠不同。他们在胚胎第18天和出生后第0天表现出高甲状腺素血症。这种围产期高甲状腺素血症伴有TH过量的表现，如大脑皮层和肝脏中受T-3正向调节的基因表达相对增加所证明。 T-4和T-3的组织积累增加以及TH替代转运蛋白（包括皮质中的Lat1、Lat2、Oatp1c1和Oatp3a1以及肝脏中的Lat2和Oatp1b2）的表达增加，表明Mct8缺陷要么直接干扰TH的组织流出，要么间接激活其他转运蛋白以增加TH的摄取。该报告首次发现 Mct8 缺陷小鼠的 TH 异常的个体发生表现为围产期 TH 过量。
Patients with the monocarboxylate transporter 8 (MCT8) deficiency syndrome present with a severe psychomotor retardation and abnormal serum thyroid hormone (TH) levels, consisting of high T-3 and low T-4 and rT(3). Mice deficient in Mct8 replicate the thyroid phenotype of patients with the MCT8 gene mutations. We analyzed the serum TH levels and action in the cerebral cortex and in the liver during the perinatal period of mice deficient in Mct8 to assess how the thyroid abnormalities of Mct8 deficiency develop and to study the thyroidal status of specific tissues. During perinatal life, the thyroid phenotype of Mct8-deficient mice is different from that of adult mice. They manifest hyperthyroxinemia at embryonic day 18 and postnatal day 0. This perinatal hyperthyroxinemia is accompanied by manifestations of TH excess as evidenced by a relative increase in the expression of genes positively regulated by T-3 in both the cerebral cortex and liver. An increased tissue accumulation of T-4 and T-3 and the expression of TH alternative transporters, including Lat1, Lat2, Oatp1c1, and Oatp3a1 in the cortex and Lat2 and Oatp1b2 in the liver, suggested that Mct8 deficiency either directly interferes with tissue efflux of TH or indirectly activates other transporters to increase TH uptake. This report is the first to identify that the ontogenesis of TH abnormalities in Mct8-deficient mice manifests with TH excess in the perinatal period.