Identification of 3,3'-T2S as a fetal thyroid hormone derivative in maternal urine in sheep

We measured 3,3'-diiodothyronine sulfate (T2S) in serum and urine (n = 5-6) obtained from euthyroid fetal (94-145 days of gestation, term = 150 days), newborn, and adult sheep and in serum and urine samples from ovine fetuses 13 days after total thyroidectomy conducted between 110 and 113 gestation days (n = 5). Sham-operated twin fetuses served as controls (n = 5). Mean serum T2S concentrations increased progressively from 94 days (74 ng/dl) to 130 days (420 ng/dl), decreasing thereafter to 145 days (197 ng/dl). T2S concentrations in fetal urine peaked at 110 days (117 ng/dl). In hypothyroid fetuses, mean serum and urine T2S were 60 and 53% of control values. To assess the possibility that the T2S in maternal serum/urine is derived from fetal serum 3,5,3'-triiodothyronine (T3), we measured T3, T3 sulfate (T3S), and T2S in fetal serum and in maternal serum and urine after bolus infusion of T3 to the fetus (n = 4). Additionally, T3, T3S, and T2S concentrations were measured in maternal serum and urine after T3 infusion to the maternal ewes (n = 4). Fetal T3 infusion rapidly increased fetal serum T3S and T2S. Maternal serum and urine T3S and T2S concentrations increased, whereas T3 concentrations remained unchanged. Maternal T3 infusion increased in serum and urine T3S and T2S levels, but the levels, relative to T3, were less than values measured after fetal T3 infusion. We conclude that T2S is a normal thyroid hormone metabolite in the ovine fetus and suggest that a major pathway of fetal T2S production is T3 to T3S to T2S.(ABSTRACT TRUNCATED AT 250 WORDS)