Schmitt C A, McDonough A A
Department of Physiology and Biophysics, University of Southern California, Los Angeles 90033.
J Biol Chem. 1988 Nov 25;263(33):17643-9.
The brain contains two molecular forms of Na,K-ATPase designated alpha found in non-neuronal cells and neuronal soma and alpha + found in axolemma. Previously we have shown that the abundance of both forms (determined by immunoblots) as well as Na,K-ATPase activity increases 10-fold between 4 days before and 20 days after birth (Schmitt, C. A., and McDonough, A. A. (1986) J. Biol. Chem. 261, 10439-10444). Hypothyroidism in neonates blunts these increases. Neonatal, but not adult brain Na,K-ATPase is thyroid hormone (triiodothyronine, T3) responsive. This study defines the period during which brain Na,K-ATPase responds to T3. The start of the critical period was defined by comparing Na,K-ATPase activity and alpha and alpha + abundance in hypothyroid and euthyroid neonates (birth to 30 days of age). For all parameters, euthyroid was significantly higher by 15 days of age. The end of the critical period was defined by dosing hypothyroid neonates with T3 daily (0.1 micrograms/g body weight) beginning at increasing days of age, and sacrificing all at 30 days then assaying enzyme activity and abundance. Those starting T3 treatment on or before day 19 were restored to euthyroid levels of Na,K-ATPase activity and abundance, while those starting T3 treatment on or after day 22 remained at hypothyroid levels of enzyme activity and abundance. We conclude that brain Na,K-ATPase alpha and alpha + isoforms are sensitive to T3 by as late as 15 days of age and that the period of thyroid hormone responsiveness is over by 22 days.
大脑中含有两种分子形式的钠钾ATP酶，分别为在非神经细胞和神经细胞体中发现的α型以及在轴膜中发现的α +型。此前我们已经表明，这两种形式的丰度（通过免疫印迹法测定）以及钠钾ATP酶活性在出生前4天到出生后20天之间增加了10倍（施密特，C.A.，和麦克多诺，A.A.（1986年）《生物化学杂志》261卷，第10439 - 10444页）。新生儿甲状腺功能减退会抑制这些增加。新生儿而非成年大脑的钠钾ATP酶对甲状腺激素（三碘甲状腺原氨酸，T3）有反应。本研究确定了大脑钠钾ATP酶对T3作出反应的时期。关键时期的开始是通过比较甲状腺功能减退和甲状腺功能正常的新生儿（出生至30日龄）的钠钾ATP酶活性以及α型和α +型的丰度来确定的。对于所有参数，甲状腺功能正常的新生儿在15日龄时显著更高。关键时期的结束是通过从不同日龄开始每天给甲状腺功能减退的新生儿注射T3（0.1微克/克体重），并在30日龄时全部处死，然后测定酶活性和丰度来确定的。那些在第19天或之前开始T3治疗的新生儿恢复到了甲状腺功能正常水平的钠钾ATP酶活性和丰度，而那些在第22天或之后开始T3治疗的新生儿则保持在甲状腺功能减退水平的酶活性和丰度。我们得出结论，大脑钠钾ATP酶α型和α +型同工型直到15日龄时仍对T3敏感，并且甲状腺激素反应期在22日龄时结束。
