Thyroid hormones and their effects: a new perspective

Abstract

The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3',5',3,5-ltetraiodothyronine (T4), 3',5,3-l-triiodothyronine (T3), 3',5',3-l-triiodothyronine (rT3) and 3,5,-ldiiodothyronine (3,5-T2). At physiological pH, dissociation of the phenolic -OH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological effects. When non-ionized these iodothyronines are strongly amphipathic. It is proposed that iodothyronines are normal constituents of biological membranes in vertebrates. In plasma of adult vertebrates, unbound T4 and T3 are regulated in the picomolar range whilst protein-bound T4 and T3 are maintained in the nanomolar range. The function of thyroid-hormone-binding plasma proteins is to ensure an even distribution throughout the body. Various iodothyronines are produced by three types of membrane-bound cellular deiodinase enzyme systems in vertebrates. The distribution of deiodinases varies between tissues and each has a distinct developmental profile. Thyroid hormones have many effects in vertebrates. It is proposed that there are several modes of action of these hormones. (1) The nuclear receptor mode is especially important in the thyroid hormone axis that controls plasma and cellular levels of these hormones. (2) These hormones are strongly associated with membranes in tissues and normally rigidify these membranes. (3) They also affect the acyl composition of membrane bilayers and it is suggested that this is due to the cells responding to thyroidhormone-induced membrane rigidification. Both their immediate effects on the physical state of membranes and the consequent changes in membrane composition result in several other thyroid hormone effects. Effects on metabolism may be due primarily to membrane acyl changes. There are other actions of thyroid hormones involving membrane receptors and influences on cellular interactions with the extracellular matrix. The effects of thyroid hormones are reviewed and appear to be combinations of these various modes of action. During development, vertebrates show a surge in T4 and other thyroid hormones, as well as distinctive profiles in the appearance of the deiodinase enzymes and nuclear receptors. Evidence from the use of analogues supports multiple modes of action. Re-examination of data from the early 1960s supports a membrane action. Findings from receptor 'knockout' mice supports an important role for receptors in the development of the thyroid axis. These iodothyronines may be better thought of as 'vitamone'-like molecules than traditional hormonal messengers. ABSTRACT The thyroid hormones are very hydrophobic and those that exhibit biological activity are 3h,5h,3,5--tetraiodothyronine (T4), 3h,5,3--triiodothyronine (T3), 3h,5h,3--triiodothyronine (rT3) and 3,5,--diiodothyronine (3,5-T2). At physiological pH, dissociation of the phenolic kOH group of these iodothyronines is an important determinant of their physical chemistry that impacts on their biological ...

The history of a developmental stage: Metamorphosis in chordates

“…They have been detected in the plasma of all vertebrates that have been tested (for detailed values, see Hulbert, 2000). In mammals and amphibians, the two main thyroid products are the stock hormone T 4 , or l-thyroxine, and the more active T 3 , or 3,3 0 ,5-triiodo-l-thyronine (iodinated 4 and 3 times, respectively) (Fig.…”

The Influence of Different Thyroid Status on Electrophysiological and Myographical Parameters of Skeletal Muscles Contraction in White Rats

“…Згідно з оцінкою ступеня вираженості голов-них симптомів зміненого тиреоїдного статусу [13,14], можна дійти висновку, що експери-менти було проведено на тваринах з двома типами індукованого гіпертиреоїдизму -лег-кого ступеня виразності (гіпертиреоз, 1-ша група) і важкого (тиреотоксикоз, 2-га група). Це було зроблено на основі визначення рек-тальної температури, швидкості споживання кисню, частоти серцевих скорочень, маси ті ла і концентрації циркулюючого вільного три-йодтироніну.…”

Endocrine factors in the hypothalamic regulation of food intake in females: a review of the physiological roles and interactions of ghrelin, leptin, thyroid hormones, oestrogen and insulin

“…The most important peripheral T 3 -producing organs are the liver, kidney and the skeletal muscle (100) . In rats, more T 3 is produced in the thyroid gland (55 %) than in other peripheral tissues (101) , while in birds almost all (99 %) T 3 is synthesised in peripheral tissues, outside of the thyroid gland (102) . The function of the thyroid gland is regulated by a negative feedback mechanism.…”

“…In piglets, thyroid hormone plasma concentration (mostly T 3 ) increases sharply after food intake, reaching its peak after 60 min. The rise in thyroid hormone concentration mainly depends on the energy content of the food and is relatively independent from the glucose concentration of the blood (101) . In contrast to feeding, starvation elicits a decrease in plasma T 3 concentration in mammals.…”

“…Carbohydrates, and to a lesser extent proteins, induce hepatic D1 gene expression (141 -143) and down-regulate D3 activity. T 3 , in turn, increases hepatic and muscular GLUT (GLUT-1 and GLUT-5) gene expression (101,144) . The latter also enhances hepatic thyroid hormone activation (145) .…”