Kilby M D, Verhaeg J, Gittoes N, Somerset D A, Clark P M, Franklyn J A
Department of Fetal Medicine, University of Birmingham, Edgbaston, United Kingdom.
J Clin Endocrinol Metab. 1998 Aug;83(8):2964-71. doi: 10.1210/jcem.83.8.5002.
Thyroid hormones are critical to growth and development of the human fetus. Abnormal placental development, a major cause of intrauterine growth restriction (IUGR), is associated with a high perinatal mortality and morbidity. Thyroid status has been postulated to play a role in the pathogenesis of such morbidity. In the present study, we have investigated fetal thyroid function and placental expression of thyroid hormone receptor (TR) alpha and beta variants during normal human pregnancy and in pregnancy associated with IUGR. Measurement of free thyroid hormones and TSH concentrations revealed significant rises in free T4 and free T3 between the second and third trimesters of normal pregnancy. Serum concentrations of free T4 and free T3 were lower in fetuses affected by IUGR, although serum TSH levels were not significantly different. Immunocytochemistry demonstrated the presence of TR alpha1, alpha2, and beta1 proteins within the nuclei of trophoblast and stromal placental cells. Immunostaining for these TR variants increased with increasing gestation in normal placenta. Comparison of IUGR placental samples with normal samples revealed greater immunostaining for TR alpha1, alpha2, and beta1 variants in IUGR. Examination of pretranslational expression of TR alpha1, alpha2, beta1, and beta2 variants by semiquantitative RT-PCR revealed increasing expression of TR alpha1, alpha2, and beta2 messenger RNAs with increasing gestation in normal pregnancy, which "mirrored" post-translational expression. However, and in contrast, there were no significant differences in expression of TR messenger RNAs in normal and IUGR placenta. The present findings of reduction in serum free thyroid hormones and increased expression of TR alpha and beta proteins in association with IUGR highlight the potential importance of thyroid status in influencing long-term fetal outcome in this condition.
甲状腺激素对人类胎儿的生长发育至关重要。胎盘发育异常是宫内生长受限（IUGR）的主要原因，与围产期高死亡率和发病率相关。甲状腺状态被推测在这种发病机制中起作用。在本研究中，我们调查了正常人类妊娠期间以及与IUGR相关的妊娠中胎儿甲状腺功能和甲状腺激素受体（TR）α和β变体的胎盘表达。游离甲状腺激素和促甲状腺激素（TSH）浓度的测量显示，正常妊娠的孕中期和孕晚期之间游离T4和游离T3显著升高。受IUGR影响的胎儿血清游离T4和游离T3浓度较低，尽管血清TSH水平无显著差异。免疫细胞化学显示滋养层和胎盘基质细胞核内存在TRα1、α2和β1蛋白。在正常胎盘中，这些TR变体的免疫染色随着妊娠进展而增加。将IUGR胎盘样本与正常样本进行比较，发现IUGR中TRα1、α2和β1变体的免疫染色更强。通过半定量逆转录聚合酶链反应（RT-PCR）检测TRα1、α2、β1和β2变体的翻译前表达，结果显示在正常妊娠中，随着妊娠进展，TRα1、α2和β2信使核糖核酸（mRNA）的表达增加，这与翻译后表达“一致”。然而，与之形成对比的是，正常胎盘和IUGR胎盘中TR mRNA的表达没有显著差异。本研究发现血清游离甲状腺激素降低以及与IUGR相关的TRα和β蛋白表达增加，突出了甲状腺状态在影响这种情况下胎儿长期结局方面的潜在重要性。
