甲状腺功能减退母亲妊娠16天和19天胎儿的核糖体蛋白合成。

Hendrich C E, Porterfield S P

Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000, USA.

Proc Soc Exp Biol Med. 1996 Dec;213(3):273-80. doi: 10.3181/00379727-213-44063.

Thyroid hormones are transported across the placenta. Thyroid hormone receptors are present in the midgestation rat fetus and fetal tissues selectively accumulate thyroid hormones prior to the onset of fetal thyroid function. It has not been demonstrated adequately that maternal thyroid hormones are essential for early fetal physiologic functions and neurological development. The present study compares the effects of maternal thyroid hormone versus fetal thyroid hormone on the regulation of rRNA and ribosomal protein synthesis in the developing fetus. This was accomplished by first comparing 16-day gestation (just prior to the onset of fetal thyroid function) fetuses of control and hypothyroid mothers. Then 19-day gestation (fetal thyroids are functional) fetuses of control and hypothyroid mothers were compared as development of fetal thyroid function lags in hypothyroid mothers. Rats made hypothyroid (Tx) by radiothyroidectomy were given replacement doses of thyroxine (T4) until the day that they were placed with a male for mating. Control, Tx and growth hormone (GH)-treated Tx dams and their fetuses were sacrificed on either the 16th or 19th day of gestation. Ribosomes (r) were isolated from placentas and from fetal brains and livers and rRNA, total 14C-leucine incorporation, and 14C-leucine incorporation into ribosomal protein per microgram of rRNA were determined. On the 16th day of gestation, prior to the onset of fetal thyroid function, all three of the above metabolic parameters were reduced significantly below control levels in the placentas of Tx rats and in the brains and livers of their fetuses. This was true also for the fetal brains and livers of GH-treated Tx mothers. Development of fetal thyroid function lags in the Tx mother. rRNA, total 14C-leucine incorporation, and 14C-leucine incorporation into ribosomal protein per microgram of rRNA continue to be significantly depressed in these fetal tissues and placentas of Tx rats on the 19th day of gestation. In fact, brain protein synthesis falls further behind in fetuses of Tx dams at this gestational age when compared with control fetal brains. These data support the hypothesis that maternal thyroid hormones are important, by at least midgestation, for normal fetal physiologic development and support the concept that appropriate maturation of the fetal pituitary-thyroid plays a role in fetal brain protein synthesis and therefore neurological development.

甲状腺激素可通过胎盘转运。甲状腺激素受体存在于妊娠中期的大鼠胎儿体内，并且在胎儿甲状腺功能开始之前，胎儿组织会选择性地蓄积甲状腺激素。目前尚无充分证据表明母体甲状腺激素对胎儿早期生理功能和神经发育至关重要。本研究比较了母体甲状腺激素与胎儿甲状腺激素对发育中胎儿rRNA和核糖体蛋白合成调节的影响。这是通过首先比较对照和甲状腺功能减退母亲的妊娠16天（刚好在胎儿甲状腺功能开始之前）的胎儿来完成的。然后比较对照和甲状腺功能减退母亲的妊娠19天（胎儿甲状腺开始发挥功能）的胎儿，因为甲状腺功能减退母亲的胎儿甲状腺功能发育滞后。通过放射性甲状腺切除术使大鼠甲状腺功能减退（Tx），并给予其替代剂量的甲状腺素（T4），直到它们与雄性大鼠交配的那天。在妊娠第16天或第19天，处死对照、Tx以及生长激素（GH）处理的Tx母鼠及其胎儿。从胎盘、胎儿脑和肝脏中分离核糖体（r），并测定rRNA、总的14C-亮氨酸掺入量以及每微克rRNA中14C-亮氨酸掺入核糖体蛋白的量。在妊娠第16天，即在胎儿甲状腺功能开始之前，Tx大鼠胎盘及其胎儿的脑和肝脏中，上述所有三个代谢参数均显著低于对照水平。接受GH处理的Tx母亲的胎儿脑和肝脏也是如此。胎儿甲状腺功能在Tx母亲体内发育滞后。在妊娠第19天，Tx大鼠的这些胎儿组织和胎盘中，rRNA、总的14C-亮氨酸掺入量以及每微克rRNA中14C-亮氨酸掺入核糖体蛋白的量仍然显著降低。事实上，与对照胎儿脑相比，在这个胎龄时，Tx母鼠胎儿的脑蛋白合成进一步落后。这些数据支持以下假设：至少在妊娠中期，母体甲状腺激素对胎儿正常生理发育很重要，并支持胎儿垂体-甲状腺的适当成熟在胎儿脑蛋白合成进而在神经发育中起作用这一概念。