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3,3',5'-triiodothyronine, (rT(3)), is easily measured in human amniotic fluid (AF) during the second and third trimesters. To determine if AF rT(3) levels are maintained by either maternal or fetal thyroid function, or both, models of fetal hypothyroidism (FH), maternal hypothyroidism (MH), and combined maternal and fetal hypothyroidism (MFH) were developed in pregnant rats. Hormone analyses of maternal and fetal serum and AF were performed at term. Thyroxine (T(4)) and 3,3',5-triiodothyronine (T(3)) were not detectable in the sera and AF of term fetuses in all groups. MFH rats were prepared by administration of methimazole to the dams, and in some experiments, by maternal thyroidectomy and a low iodine diet as well. In the MFH groups from the three experiments serum thyrotropin (TSH) was markedly elevated in the dams and in the fetuses. FH rats were prepared by administering T(4) by various routes to dams treated according to the MFH protocols and serum TSH was elevated in fetal serum. Analysis of FH maternal serum T(4), T(3), and TSH concentrations suggested mild maternal hyperthyroidism or hypothyroidism depending upon the schedule of T(4) administration. The MH groups were prepared by maternal thyroidectomy and in all experiments the fetuses had normal serum TSH concentrations. The degree of maternal hypothyroidism in the MH and MFH groups was equivalent. The mean concentration of AF rT(3) in normal rats in three experiments was 28.4+/-2.5 ng/dl (+/-SEM). In the three experiments, AF rT(3) was undetectable or markedly reduced in the MH and MFH rats and was normal in the FH rats. These results in the amniotic fluid could not be explained by transfer of rT(3) from fetal serum to the AF because fetal serum rT(3) concentrations in these various models did not correlate with AF rT(3) concentration. Furthermore, infusion of large doses of rT(3) in MFH dams resulted in a 35-fold elevation in maternal serum rT(3) concentration, a twofold elevation in fetal serum rT(3) concentration, and only a minimal increase in AF rT(3). These studies demonstrated that, in the rat, the maternal thyroid has the dominant role in maintaining AF rT(3), whereas little effect of fetal thyroid status on AF rT(3) could be demonstrated. Transfer of maternal rT(3) or of fetal rT(3) derived from maternal T(4) to the AF do not appear to be the mechanisms whereby the maternal thyroid maintains AF rT(3).

Maternal Thyroid Function is the Major Determinant of Amniotic Fluid 3,3′,5′-Triiodothyronine in the Rat