Thyroid Hormone Receptors in the Developing Rat Brain

It is widely believed that the adult mammalian brain is insensitiveto thyroid hormones unlike the neonatal brain which is criticallydependent on these hormones for the development of normal structureand function. Recent studies have demonstrated the presenceof limited capacity, high affinity, triiodothyronine (T3) bindingnuclear sites in tissues that are considered responsive to thyroidhormones. Furthermore, there is evidence from studies on peripheraltissues that these T3 binding sites act as true receptors ininitiating thyroid hormone action. This report examines whetherthe higher sensitivity of neonatal brain to thyroid hormonesand the purported decline in sensitivity in adulthood are relatedto changes in the concentration and affinity characteristicsof thyroid hormone receptors in rat cerebral nuclei. Analysisof Scatchard plots of in vitro T3 binding data indicate thatcerebral nuclei from adult rats contain T3 specific nuclearbinding sites at a concentration comparable to that presentduring the period when the brain is critically dependent onthe presence of thyroid hormones and exceed that in the liver,a tissue generally considered thyroid sensitive. Neonatal thyroidectomysignificantly increased the number of binding sites. The resultsshow that the apparent unresponsiveness of the cerebral cortexof adult rats to thyroid hormones is not due to the absenceor a low density of T3 nuclear binding sites. The significanceof these results is discussed.