Prenatal Exposure of the Fetal Rat to Excessive L-Thyroxine or 3,5-Dimethyl-3′-Isopropyl-Thyronine Produces Persistent Changes in the Thyroid Control System

Summary

Studies were conducted to determine if brief exposure, in utero, to high levels of T₄ or to the synthetic thyromimetic agent 3,5-dimethyl-3′-isopropyl-L-thyronine (DIMIT) can produce permanent disruption of the thyroid control system in a manner analogous to the changes in the “set point” reported to occur due to neonatal T₄ exposure in the “neo-T₄ syndrome”. If such a change were to occur, it could explain the persistent thyroid disturbances seen in the progeny of hypothyroid mother rats. These latter progeny are exposed in utero to both low and high serum T₄ levels.

Maternal T₄ treatment produced a 4-fold elevation in fetal serum T₄ accompanied by a large decrease in serum TSH levels. The brief treatment in utero with high doses of T₄ or of DIMIT resulted in higher neonatal mortality and the T₄-treatment produced subsequent growth stunting. These treatments resulted in suppression of the fetal/neonatal thyroid which was very apparent at 5 days of age. At 30 days postpartum, the thyroid control system of the progeny of the T₄ and DIMIT-treated animals was still abnormal with low serum T₄ levels accompanied with normal serum TSH and T₃ levels. At 60 days of age, serum T₄ levels remained low in the progeny of the T₄-treated animals and the TSH response to TRH was subnormal in both the progeny of the T₄-treated and the DIMIT-treated animals. However, serum and pituitary TSH and serum T₃ were normal.

The thyroid control system of the rat is sensitive to prenatal exposure to hyperthyroxinemia as it is to postnatal exposure. While the T₄ and DIMIT-treated pups resembled the pups of thyroidectomized (Tx) dams in some respects, they did not show the inability to maintain normal serum T₃ levels as seen in the progeny of the Tx mothers.

Key-Words:

Maternal-Fetal-Thyroid-Neo-T ₄ Syndrome