Physiological Effects of Thyroid Hormones

Chemical Structure and Calorigenic Potency of Thyroid Hormones in 

The Entry of Tliyroid Hormones into Cells and Their Intracellular Distribution. 258 

Interaction of Thyroid Hormones with Metal Ions. 270 

The mechanism of action of the thyroid hormone, or hormones, has interested investigators since the turn of the century, when the properties of the thyroid secretions first began to be appreciated. The problem was approached initially as it related to the whole animal or to specific organs or tissues more recently extensive investigation has been conducted at the level of the cell and its constituents, in particular the subcellular particles and certain enzymes. 

The physiological effects of the thyroid secretions in mammals appear to be well established. There is, however, no general agreement on the structure of the molecule responsible for hormonal activity in the peripheral tissues, nor on the exact mechanism of action at the subcellular level. This review will concern itself with the current status of these two problems as they apply to mammals. 

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Because of the role of mitochondria in cellular respiration and energy production, efforts to elucidate the mechanism of thyroid hormone action in metabolism and calorigenesis have focused on mitochondrial studies. Thyroid hormones in vitro are known to uncouple oxidative phosphorylation in isolated mitochondria, but these effects occur at unphysiological doses of T4. In physiological concentrations, T4 increases adenosine triphosphate (ATP) formation and the number and inner membrane surface area of mitochondria (21), but T4 does not reduce the efficiency of oxidative phosphorylation. Furthermore, 2,4-dinitrophenol, a classic uncoupler of oxidative phosphorylation, can neither relieve hypothyroidism nor duplicate other physiological effects of thyroid hormones. 

Since the brain contains receptors and is a developmental and homeostatic target for thyroid hormones, a mechanism must exist which discriminates between neural and peripheral tissue-specific functions under thyroid hormone control. We describe here the properties of a thyroid hormone receptor predominantly expressed in the rat brain. We also present in situ hybridization histochemistry data outlining the brain subregions containing this receptor mRNA. Its characterization implies a multiple receptor system which may help to explain some of the tissue-specific physiological effects of thyroid hormones. 

Anterior Lobe. The anterior pituitary, or adenohypophysis, secretes six important peptide hormones. The anterior pituitary releases growth hormone (GH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), and prolactin (Pr). The physiologic effects of these hormones are listed in Table 28-1. 

These receptors are chiefly responsible for the physiological effects of steroid hormones such as cortisol as well as thyroid hormone and vitamin A. They are proteins that share a common basic structure consisting of a ligand binding domain and a DNA binding domain (comprised of zinc finger motifs). They operate as ligand-responsive transcription factors (see Chap. 17 for further discussion). 

M16. Moses, C., Sunder, J. H., Vester, J. W., and Donowski, T. S., Hydrocortisone and/or desiccated thyroid in physiological dosage. XI. Effects of thyroid hormone excesses on lipids and other blood and serum solutes. Metab., Clin. Exptl. 13, 717-728 (1964). 

Only those physiologic actions of thyroid hormone that influence fuel metabolism are considered here. It is important to stress the term physiologic, because the effects of supraphysiologic concentrations of thyroid hormone on fuel metabolism may not be simple extensions of their physiologic effects. In general, the following... 

Because in most physiological circumstances oxygen consumption is controlled by energy metabolism, Ismail-Beigi and Edelman (22) proposed that the primary effect of thyroid hormones is to increase the amount of energy expended in translocating cations across cell membranes, probably as a response to an increased passive leak of sodium into, and potassium out of, cells. The extent to which this transport contributes to heat production and ATP utilization is uncertain. The stimulation of futile cycles by thyroid hormones (23) has been suggested to be an additional component of ATP disposal. 

Hoch, F.L. 1974. Metabolic effects of thyroid hormones. In Handbook of Physiology, Section 7 Endocrinology (M.A. Greer and D.H. Solomon, eds), pp. 391-412. American Physiological Society, Washington, DC. 

Physiologic Function Testing, An example of this application is the assay of thyroid hormone levels in (lie blood winch, in turn, can aid in the assessment of thyroid function. The radioactive iodine uptake test, which involves the administration of a dose of l31l (iodine-131) to the patient, is also a valuable procedure in assessing thyroid function. At present, the technique is best reserved for problem cases rather than used as a primary screening test. The main disadvantage of this test is the effect of the dietary intake of iodine, which reacts in various ways in different individuals. 

The many effects of lithium on thyroid physiology and on the hypothalamic-pituitary axis and their clinical impact (goiter, hypothyroidism, and hyperthyroidism) have been reviewed (620). Lithium has a variety of effects on the hypothalamic-pituitary-thyroid axis, but it predominantly inhibits the release of thyroid hormone. It can also block the action of thyroid stimulating hormone (TSH) and enhance the peripheral degradation of thyroxine (620). Most patients have enough thyroid reserve to remain euthyroid during treatment, although some initially have modest rises in serum TSH that normalize over time. 

The noted positive physiological effects of reasonable dosages of thyroid hormones included ... 

Endocrine Effects. Selenium is a component of all three members of the deiodinase enzyme family, the enzymes responsible for deiodination of the thyroid hormones, and has a physiological role in the control of thyroid hormone levels. Significant decreases in triiodothyronine levels in response to elevated selenium have been observed in humans. However, the triiodothyronine levels observed in these studies were within the normal human range, so the biological impact of this change is unclear. 

In mammals the physiological actions of the thyroid hormones are multiple, and it is still not clear wheth< r or not they are manifestations of but a single action at the cellular level. Calorigcnesis is the effect of the hormones which has been most exten.sively investigated. It will be discussexl in detail below. 

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