Thyroxine Metabolism and Thyroid Function in the Pregnant Rat

Thyroxine (T4) metabolism and thyroid function were assessed in the pregnant rat. During the last few days of pregnancy, the urinary excretion of 131I, determined in rats isotopically equilibrated with 131I-T4 (0.5-2 Mg/100 g body weight/day), and expressed either in absolute terms or as a percentage of the administered dose, was greatly increased. This indicated an increase not only in the amount, but also in the rate of excretion of iodide derived from T4. The increase was associated with a marked fall in the concentration of T4 in serum. Thus, the clearance of T4 from plasma was greatly enhanced. The increased clearance was due not only to an enhanced rate of deiodination, but also to an increased clearance by the gastrointestinal pathway. After delivery the urinary excretion of iodide was no longer increased and the serum T4 concentration returned to normal within a few days. Studies of T4 metabolism in vitro indicated that, although hepatic deiodinating activity was normal in the 20-day pregnant rat, it was high in comparable preparations of fetal tissue. In serum, the T4-binding activity was reduced, the proportion of unbound T4 was increased and the absolute concentration of free T4 was normal during pregnancy. Thyroid activity, as indicated by the absolute rate of uptake of iodide by the thyroid, was slightly increased in late pregnancy although not enough to maintain a normal PBI. It was concluded that pregnancy in the rat is associated with an increase in the fractional and probably the absolute rate of turnover of T4 in the tissues. The increase is due in part to alterations in the T4-binding activity in serum, and may also result from hormonal deiodination in fetal tissues. (Endocrinology82: 282, 1968)