Regulation of metallothionein-3 mRNA by thyroid hormone in developing rat brain and primary cultures of rat astrocytes and neurons.

Metallothionein-3 (MT-3) is a brain specific member of the MT family. Unlike other members of this family, MT-3 has been shown to act as a neuronal growth inhibitory factor. MT-3 mRNA abundance increases throughout the developmental period, reaching adult levels by postnatal day 21. The role of thyroid hormone in the developmental regulation of MT-3 mRNA was tested because thyroid hormone is known to regulate brain gene expression. Furthermore, gestational hypothyroidism results in developmental brain abnormalities. Hypothyroidism was induced in pregnant dams by the administration of PTU from gestational day 7, resulting in a 4- to 6-fold increase in pup MT-3 mRNA abundance on the day of birth (day 0) and on postnatal day 3. Normal pups did not reach this level of brain MT-3 mRNA until postnatal day 21. Administration of thyroxine (T(4), 2 microg/g) to pups on postnatal day 1 or day 20 resulted in a decrease in MT-3 mRNA abundance on postnatal day 21, regardless of when the injection was given. Furthermore, addition of T(4) to primary cultures of brain (olfactory bulb) astrocytes and neurons from 4-day-old rats resulted in a significant decrease in MT-3 mRNA in 24 h. Given the neuronal growth inhibitory function of MT-3, these data suggest that MT-3 may play a role in the CNS-related consequences of hypo- and hyperthyroidism during development. Copyright 1999 Elsevier Science B.V.