Thyroid hormone uptake by rat hepatocytes in primary culture

textabstractIodide is taken up by the thyroid follicular cell, oxydized and bound to thyroglobulin at the apical membrane facing the colloid in the follicular lumen. Iodinated colloid is subsequently engulfed by the follicular cell and hydrolysed, liberating thyroxine and triiodothyronine from their peptide linkage to thyroglobulin. Iodothyronines are then secreted into the blood stream. These and other steps in the synthesis and secretion of thyroid hormones are conditioned by the extent of thyroid stimulation by pituitary thyrotropin. The synthesis and release of thyrotropin is stimulated by the hypothalamic thyrotropinreleasing hormone, while thyroid hormone inhibits these processes (Larsen, 1982). In this way, a negative feedback mechanism is formed between the thyroid and pituitary. The main product secreted by the human thyroid is thyroxine (mean 115 nmol/day per 70 kg body weight). Other products are triiodothyronine (mean 9 nrnol/day, which accounts for 20% of the total daily production) and reverse triiodothyronine (mean 2 nmol/day; 6%) (Chopra, 1976; Chopra et al., 1978a; Visser, 1980). From these figures it will be clear that synthesis of the latter iodothyronines occurs mainly outside the thyroid gland by monodeiodination of thyroxine, the so-called peripheral production. In pathophysiological conditions, like iodine deficiency and Graves' disease, thyroidal secretion of triiodothyronine is increased relative to that of thyroxine (Izumi and Larsen, 1977). The relative contribution of different tissues to the daily production of triiodothyronine and reverse triiodothyronine is at present unknown. However, deiodination has been observed in vitro in almost all tissues studied (see review by Visser, 1980). Based on circumstantial evidence, it is generally believed that the liver is the main site of triiodothyronine synthesise For instance, in liver cirrhosis triiodothyronine production is decreased, while apparent reverse triiodothyronine synthesis is unaltered (Chopra, 1976). The latter finding is in favour of extra-hepatic thyroxine_.reverse triiodothyronine conversion. The low serum reverse triiodothyronine levels in patients with severe, chronic renal failure may suggest that substantial amounts of reverse triiodothyronine are produced in the kidneys (Chopra et al., 1975; Weissel et al., 1977; Weissel and Stummvoll, 1981)