THYROID HORMONES AND THE REGULATION OF BIOCHEMICAL PROPERTIES OF NERVOUS TUMOR CELL LINE

The regulatory role of thyroid hormones in growth and development of the neural tissue is well established through morphological, biochemical and behavioral studies. However, despite evidence from peripheral tissue that T3 nuclear receptors act as a primary site of initiation of thyroid function, the nature of this regulation in neural tissue remains unclear. Although high affinity, low capacity binding sites for T3 have been detected in the developing and mature brain, a direct receptor-biological effect relationship has not been demonstrated as, for example, a direct relation to neurotransmission.;In order to define some of the biochemical aspects of thyroidal involvement in the regulation of brain function, a tissue culture system composed of two neuroblastoma cell lines has been used in this study. Attempts have been made to define direct versus indirect effects of thyroid hormone on the biochemical properties of neuroblastoma cells A2(1) and (')E by measuring the levels of T3 nuclear receptors, catecholamine synthesizing (tyrosine hydroxylase) and degradative (monoamine oxidase) enzymes, RNA, DNA, and protein, under eu- and hypothyroid conditions. The relationship between the nuclear receptor occupancy by T3 and the induction of tyrosine hydroxylase in (')E cell line has also been examined. Another part of this work involves the relationship between thyroid hormone and neuronal differentiation, induced by sodium-butyrate. The results of this study indicate that thyroid hormone is directly involved in the regulation of biochemical properties of neural cells.;Neuroblastoma cells grown in hypothyroid medium showed a retarded rate of growth and lower levels of RNA and protein content compared to the ones grown in euthyroid medium. In both cell lines studied the activities of tyrosine hydroxylase and monoamine oxidase were significantly lower in hypothyroidism compared to euthyroidism. T3 nuclear receptors increased significantly in hypothyroidism, an increase which indicates that thyroid hormone down regulates the levels of its receptors. Also the amount of T3 bound to the nuclear receptors showed a good correlation with the induction of tyrosine hydroxylase by thyroid hormones in the (')E cell line. This correlation supports the idea that nuclear receptors are the primary site of initiation of thyroid hormone action in neural tissue. Sodium-butyrate treatment induced chemical differentiation in neuroblastoma cells as indicated by increased protein, RNA, and activities of catecholaminergic enzymes. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI.