Thyroid hormone action in the cell.

THYROID HORMONES have profound effects on the growth, development, and metabolism of many tissues of higher organisms [1]. Although the biochemical bases of these effects are not fully understood, the regulation of protein synthesis is a primary event [1]. After binding to nuclear receptors, thyroid hormones control the accumulation of specific mRNA molecules that code for the synthesis of specific proteins regulated by the hormone. Human and rat thyrotropin (TSH) [2], rat growth hormone (rGH) [3], rat hepatic spot 14 [4], rat hepatic malic enzyme [5], and rat and rabbit heart myosin heavy chain [6] are examples in which the immediate regulation of gene expression by thyroid hormone is reported. The principal thyroid hormones are L-thyroxine (T4) and 3,5,3'-triiodo-L-thyronine (T3). T3 is almost 10 times more biologically active than T4 [7] and virtually all of the metabolic action of T4 can be ascribed to the action of T3 that it gives rise to. T4 is present in human serum at about 110 nmol/ liter. Most of it is bound by serum proteins, but 0.03% is in a free form [8]. T3 is present in human serum at about 2.1 nmol/liter, 85% of which comes from the deiodination of T4 in peripheral tissues [8]. About 0.3% of serum T3 is in a free form and it is this fraction that is taken up by the cells to exert physiological effects [9]. Thyroid hormones are taken up by the cell through an energy-dependent, saturable process or by passive diffusion [10-12] before they are metabolized or exert biological activity. In some tissues such as the central nervous systems, pituitary gland, and brown adi-