Different Regulation of Thyroid Hormone Transport in Liver and Pituitary: Its Possible Role in the Maintenance of Low T3 Production during Nonthyroidal Illness and Fasting in Man

Abstract

Nonthyroidal illness (NTI) and fasting in man are characterized by a low serum concentration of T3 and an increased serum concentration of rT3. Since the serum level of T3 is one of the most important factors that determine the metabolic rate, the low serum T3 during NTI or fasting results in reduction of the energy consumption of the body. This can be regarded as an adaptive mechanism to save energy, and thus to conserve protein and to protect organ function. The low serum T3 concentration should preferentially be maintained until recovery from illness or adequate calorie supply. This implies that the low serum T3 should not result in a rise in serum TSH. We postulate that different regulation of thyroid hormone transport into the relevant tissues, i.e., liver and pituitary, may play a role in maintenance of the low T3 production during NTI and fasting. This hypothesis is further elaborated in this paper by comparing (i) the properties of the thyroid hormone uptake mechanism in rat and human hepatocytes, perfused rat liver, and rat anterior pituitary cells, and (ii) the effects of fasting and conditions that mimic NTI on thyroid hormone transport in the same preparations. In addition, the consequences of changes in thyroid hormone transport and peripheral thyroid hormone metabolism during fasting and NTI for the serum level of rT3 and for TSH secretion are discussed. The data are compatible with the existence of different transport systems for thyroid hormone in liver and pituitary. We suggest that these different thyroid hormone carriers allow tissue-specific regulation of the intracellular availability of T3.

Uptake of triiodothyronine and triiodothyroacetic acid in neonatal rat cardiomyocytes: effects of metabolites and analogs

“…We have previously compared uptake mechanisms for thyroid hormones in pituitary and liver, and postulated that regulation of the transport in these two tissues was different (Everts et al 1996a). This difference could play a part in maintenance of the low serum T 3 and normal TSH concentrations in non-thyroidal illness and fasting (Everts et al 1996a, Hennemann et al 1998. When the present data are compared with the results obtained in pituitary cells (Everts et al 1994(Everts et al , 1995, it seems that the transport mechanism for T 3 into the heart is different.…”

“…When the present data are compared with the results obtained in pituitary cells (Everts et al 1994(Everts et al , 1995, it seems that the transport mechanism for T 3 into the heart is different. Whether T 3 uptake in heart is similar or different as compared with that in liver (Everts et al 1996a) remains to be established. This question is of relevance to the development of drugs with tissue-selective thyromimetic activity (Ichikawa et al 2000, Trost et al 2000.…”

“…Kragie (1994) and Hennemann et al (2001) have reviewed the properties of thyroid hormone transport mechanisms in many cell types. We have previously compared uptake mechanisms for thyroid hormones in pituitary and liver, and postulated that regulation of the transport in these two tissues was different (Everts et al 1996a). This difference could play a part in maintenance of the low serum T 3 and normal TSH concentrations in non-thyroidal illness and fasting (Everts et al 1996a, Hennemann et al 1998.…”

“…In view of the significance of plasma membrane transport for the bioavailability of thyroid hormones (Hennemann et al 1998, and the possible existence of different transport systems in different tissues (Kragie 1994, Everts et al 1996a, we have previously explored the thyroid hormone transport system in the heart (Everts et al 1996b, Van der Putten et al 2001, Verhoeven et al 2001. In the present study we continued this work by comparing the uptake of [ …”

Uptake of tri-iodothyronine and thyroxine in myoblasts and myotubes of the embryonic heart cell line H9c2(2-1)

“…This is different from the situation in the liver, where separate carriers are presumably involved in uptake of T 3 and T 4 (Krenning et al 1981). These differences suggest that thyroid hormone uptake is regulated in a tissue-specific manner, which may significantly influence total thyroid hormone bioactivity (Everts et al 1996a, Hennemann et al 1998, 2001). The H9c2(2-1) cell line is frequently used as a model for cardiac myocytes (Eckel 1996, Brostrom et al 2000, Wayman et al 2001.…”