Regulation of iodothyronine deiodinases in the Pax8-/- mouse model of congenital hypothyroidism
Regulation of iodothyronine deiodinases in the Pax8-/- mouse model of congenital hypothyroidism
复制标题
DOI：
10.1210/en.2002-220715
复制
发表时间：
2003-03-01
期刊：
影响因子：
4.8
通讯作者：
Visser, TJ
中科院分区：
文献类型：
--
作者：
Friedrichsen, S;Christ, S;Visser, TJ
甲状腺激素对于各种发育和代谢过程至关重要。先天性甲状腺功能减退症（CHT）会导致不同组织（特别是大脑）发育的严重缺陷。作为 CHT 的动物模型，我们研究了 Pax8(-/-) 小鼠，这种小鼠出生时没有甲状腺。我们测定了 Pax8(-/-) 与对照小鼠在生命的前 3 周期间肝脏和肾脏中碘甲状腺原氨酸脱碘酶 D1、脑和垂体中 D2 和脑中 D3 的表达，以及血清 T-4、T-3 和 rT(3) 水平。在对照小鼠中，血清 T-4 和 T-3 在出生当天（第 0 天）检测不到，并在第 15 天增加至最高水平。在 Pax8(-/-) 小鼠中，血清 T-4 和 T-3 仍低于检测限。两组小鼠的血清 rT(3) 在第 0 天均较高，而 Pax8(-/-) 小鼠的血清 rT(3) 迅速下降，但对照组小鼠则不然。肝脏和肾脏 D1 活性和 mRNA 水平在第 0 天较低，而对照小鼠中的升高与血清 T-4 和 T-3 水平大致平行。在 Pax8(-/-) 小鼠中，组织 D1 活性和 mRNA 水平仍然较低。大脑 D2 活性在第 0 天较低，并在第 15 天增加到最高水平，Pax8(-/-) 小鼠的大脑 D2 活性比对照小鼠高约 10 倍。仅在第 21 天，Pax8(-/-) 中的 D2 mRNA 水平高于对照小鼠。大脑 D3 活性和 mRNA 水平在第 0 天时较高，并在第 3 至 15 天之间适度下降，Pax8(-/-) 中的值略低于对照小鼠。注射 200 ng T-4 或 20 ng T-3/g 体重一天后，组织脱碘酶活性和 mRNA 水平至少部分恢复至对照水平，但脑 D3 活性除外。总之，这些发现表明，在生命的前 3 周内，小鼠中枢和外周组织中脱碘酶的表达发生了显着的年龄和甲状腺状态依赖性变化。
Thyroid hormones are essential for a variety of developmental and metabolic processes. Congenital hypothyroidism (CHT) results in severe defects in the development of different tissues, in particular brain. As an animal model for CHT, we studied Pax8(-/-) mice, which are born without a thyroid gland. We determined the expression of iodothyronine deiodinase D1 in liver and kidney, D2 in brain and pituitary, and D3 in brain, as well as serum T-4, T-3, and rT(3) levels in Pax8(-/-) vs. control mice during the first 3 wk of life. In control mice, serum T-4 and T-3 were undetectable on the day of birth (d 0) and increased to maximum levels on d 15. In Pax8(-/-) mice, serum T-4 and T-3 remained below detection limits. Serum rT(3) was high on d 0 in both groups and rapidly decreased in Pax8(-/-), but not in control mice. Hepatic and renal D1 activities and mRNA levels were low on d 0 and increased in control mice roughly parallel to serum T-4 and T-3 levels. In Pax8(-/-) mice, tissue D1 activities and mRNA levels remained low. Cerebral D2 activities were low on d 0 and increased to maximum levels on d 15, which were approximately 10-fold higher in Pax8(-/-) than in control mice. D2 mRNA levels were higher in Pax8(-/-) than in control mice only on d 21. Cerebral D3 activities and mRNA levels were high on d 0 and showed a moderate decrease between d 3 and 15, with values slightly lower in Pax8(-/-) than in control mice. One day after the injection of 200 ng T-4 or 20 ng T-3/g body weight, tissue deiodinase activities and mRNA levels were at least partially restored toward control levels, with the exception of cerebral D3 activity. In conclusion, these findings show dramatic age and thyroid state-dependent changes in the expression of deiodinases in central and peripheral tissues of mice during the first 3 wk of life.