CIRCULATING THYROID-HORMONE CONCENTRATIONS AND PLACENTAL THYROID-HORMONE RECEPTOR EXPRESSION IN NORMAL HUMAN-PREGNANCY AND PREGNANCY COMPLICATED BY INTRAUTERINE GROWTH RESTRICTION (IUGR)

Thyroid hormones are critical to growth and development of the human f etus. Abnormal placental development, a major cause of intrauterine gr owth restriction (IUGR), is associated with a high perinatal mortality and morbidity. Thyroid status has been postulated to play a role in t he pathogenesis of such morbidity. In the present study, we have inves tigated fetal thyroid function and placental expression of thyroid hor mone receptor (TR) alpha and beta variants during normal human pregnan cy and in pregnancy associated with IUGR. Measurement of free thyroid hormones and TSH concentrations revealed significant rises in free T-4 and free T-3 between the second and third trimesters of normal pregna ncy. Serum concentrations of free T-4 and free T-3 were lower in fetus es affected by IUGR, although serum TSH levels were not significantly different. Immunocytochemistry demonstrated the presence of TR alpha 1 , alpha 2, and beta 1 proteins within the nuclei of trophoblast and st romal placental cells. Immunostaining for these TR variants increased with increasing gestation in normal placenta. Comparison of IUGR place ntal samples with normal samples revealed greater immunostaining for T R alpha 1, alpha 2, and beta 1 variants in IUGR. Examination of pretra nslational expression of TR alpha 1, alpha 2,beta 1, and beta 2 varian ts by semiquantitative RT-PCR revealed increasing expression of TR alp ha 1, alpha 2, and beta 2 messenger RNAs with increasing gestation in normal pregnancy, which ''mirrored'' post-translational expression. Ho wever, and in contrast, there were no significant differences in expre ssion of TR messenger RNAs in normal and IUGR placenta. The present fi ndings of reduction in serum free thyroid hormones and increased expre ssion of TR alpha and beta proteins in association with IUGR highlight the potential importance of thyroid status in influencing long-term f etal outcome in this condition.