Iodothyronine-5′-Deiodinase Activity in Progenies of Hypothyroid Rats

Summary

Iodothyronine-5′-deiodinase activity (I-5′-DA) was measured in the progenies of control rats, hypothyroid (Tx) rats, and hypothyroid treated with ovine GH (Tx + GH) during gestation. The enzyme was measured in cerebral cortex and cerebellum at 22 days gestation and at 5, 10, 30 and 60 days postpartum. In addition, the pituitary I-5′-DA was assessed in the postnatal animals. The experiments were undertaken because the tissues of the progenies of rats that were hypothyroid during pregnancy appeared in many ways to resemble those of hypothyroid animals, even at ages when serum thyroxine (T₄) and triiodothyronine (T₃) levels were normal. It was found that the progenies of Tx mothers had low liver 5′-deiodinase activities. This is a likely cause of the low serum T₃ levels with normal T₄ levels seen in these progenies in the neonatal period. Cerebral and cerebellar 5'-deiodinase activities were low in these progenies during the thyroid hormone-dependent perinated period of brain development. The progenies of GH-treated Tx dams had higher enzyme activities than the progenies of untreated Tx dams. These pups from GH-treated Tx mothers have been shown previously to have significantly less neurological impairment than the progenies of untreated Tx mothers. As most of the brain intracellular T₃ is produced in situ, a functional thyroid deficiency could result from such a 5′-deiodinase deficiency. As the deiodinase deficiency was still seen in the progenies of Tx mothers at 60 days of age, such a deficiency could explain why, even though serum T₄ and T₃ levels were normal, brain metabolism was in many ways characteristic of hypothyroidism. Pituitary I-5′-DA of the progenies of Tx mothers was not significantly different from that of controls. These results do not explain the observation that serum TSH levels are high and T₄ and T₃ levels are normal in the 60 day old progenies of Tx mothers.

Key-Words

Hypothyroid Rats - Iodothyronine-5′-Deiodinase - Cerebrum - Cerebellum - Liver - Pituitary