Effect of Thyroid Hormone Deficiency on RC3/neurogranin MRNA Expression in the Prenatal and Adult Caprine Brain

Thyroid hormone deficiency has profound effects on the brain during development and less marked effects on the adult brain. These effects are considered to be the result of the direct regulation of specific target genes by thyroid hormone. Previous studies have shown that the expression of the neuronal gene RC3, encoding a 78-amino-acid calmodulin-binding protein kinase C substrate, is under the influence of thyroid hormone in vivo. In congenitally hypothyroid foetal goat at term (approximately 150 days of gestation), RC3 mRNA expression was reversibly decreased in the striatum but not in other brain regions. In the present study we investigated the role of thyroid hormone in RC3 mRNA expression at earlier stages of fetal development and in mature goats using in situ hybridization. There was a consistent decrease (35-80%) in the signal for RC3 mRNA per neuron in the striatum of hypothyroid adult and fetal goats of 90, 120 and 150 days of gestation compared to normal goats of the same age. In contrast, no consistent difference was observed in the cerebral cortex at any age studied. These data indicate that in both fetal and adult goats thyroid hormone, at least partly, affects the expression of RC3 mRNA in the striatum and not the cerebral cortex.