Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations
Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations
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DOI：
10.1210/en.2010-0252
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发表时间：
2010-08-01
期刊：
影响因子：
4.8
通讯作者：
Anderson, Grant W.
中科院分区：
文献类型：
--
作者：
Bastian, Thomas W.;Prohaska, Joseph R.;Anderson, Grant W.
铜 (Cu)、铁 (Fe) 和碘/甲状腺激素 (TH) 缺乏会导致大脑发育后期出现类似的缺陷，这表明这些微量营养素缺乏有一个共同的机制，导致观察到的紊乱。先前对啮齿动物（断奶后和成人）和人类（青少年和成人）的研究表明，铜和铁缺乏会影响下丘脑-垂体-甲状腺轴，导致 TH 状态改变。然而，重要的是，尚未在最脆弱的人群（发育中的胎儿/新生儿）中评估铁和铜缺乏与甲状腺状态之间的关系。我们假设铜和铁的缺乏会降低发育过程中的循环和大脑 TH 水平，从而导致与这些缺陷相关的大脑发育缺陷。为了检验这一假设，怀孕的母鼠从妊娠早期到断奶期间都缺乏铜（CuD）、FeD或TH。随后在出生后第 12 天 (P12) 幼崽中测量血清甲状腺素 (T-4) 和三碘甲状腺原氨酸 (T-3) 以及脑 T-3 水平。铜缺乏使 P12 时血清总 T-3 减少 48%，血清总 T-4 减少 21%，全脑 T-3 减少 10%。缺铁使 P12 时血清总 T-3 减少 43%，血清总 T-4 减少 67%，全脑 T-3 减少 25%。大脑 mRNA 分析显示，CuD 或 FeD 新生儿中几个 TH 反应基因的表达发生了改变，这表明 FeD 和 CuD 新生儿大脑感知到 TH 浓度降低。这些结果表明，至少一些与新生儿铁和铜缺乏相关的大脑缺陷是通过循环和大脑 TH 水平的降低介导的。 （内分泌学151：4055-4065，2010）
Copper (Cu), iron (Fe), and iodine/thyroid hormone(TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T-4) and triiodothyronine (T-3), and brain T-3 levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T-3 by 48%, serum total T-4 by 21%, and whole-brain T-3 by 10% at P12. Fe deficiency reduced serum total T-3 by 43%, serum total T-4 by 67%, and whole-brain T-3 by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that atleast some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels. (Endocrinology 151: 4055-4065, 2010)