Thyroid hormones physiological effects

The TAAR receptor system has also been associated with body temperature regulation on the basis of putative thyroid hormone metabolites and their synthetic derivatives (thyronamines) activating TAAR1 in rodents. However, as these effects are only observed with thyronamine concentrations several orders of magnitude above physiological levels, and as the specificity of these compounds has not been determined, the physiological significance of these observations is unclear. 

The thyroid hormones are lipophilic and relatively insoluble in the plasma. Therefore, they are transported throughout the circulation bound to plasma proteins such as thyroxine-binding globulin (75%) and albumins (25%). Approximately 99.96% of circulating thyroxine is protein bound. Bound hormone is not available to cause any physiological effects however, it is in equilibrium with the remaining 0.04% that is unbound. This free form of the hormone is able to bind to receptors on target tissues and cause its effects. Thyroid hormone has many metabolic effects in the body ... 

Retinoids are a family of naturally occurring and synthetic analogues of vitamin A. The skin of subjects deficient in vitamin A becomes hyperplastic and keratotic (phrynoderma, or toad skin). While natural vitamin A is occasionally employed therapeutically, synthetic retinoids are more effective and represent a major advance in dermatological pharmacotherapy. Retinoids have myriad effects on cellular differentiation and proliferation it is likely that nuclear retinoic acid receptors mediate these effects by activating gene expression in a manner analogous to receptors for steroid hormones and thyroid hormones. Despite a common mechanism of action, however, retinoids vary widely in their physiological effects. 

Most attempts of using hormones as psychotropic medications were conducted with gonadal or with thyroid hormones, mainly because of the apparent mood changes associated with physiological or disorder-associated changes in levels or activity of these hormones. However, as shown in Table 17-1, current applications are broader and involve several hormones and systems. It is anticipated that, with acquired knowledge on mood effects of several other hormones, that list will continue to expand. Here, I focus on psychotropic effects of gonadal and thyroid hormones. Cortisol and melatonin are only briefly discussed. 

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 ... 

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. 

Because thyroxine contains four iodine residues, this compound is also referred to by the abbreviation T4. Likewise, triiodothyronine contains three iodine residues, hence the abbreviation T3. There has been considerable discussion about which hormone exerts the primary physiologic effects. Plasma levels of T4 are much higher than T3 levels, but T3 may exert most of the physiologic effects on various tissues, which suggests that T4 is a precursor to T3 and that the conversion of T4 to T3 occurs in peripheral tissues.23 Regardless of which hormone ultimately affects cellular metabolism, both T4 and T3 are needed for normal thyroid function. 

Parker, S.J. and Specker, J.L. (1990). Salinity and temperature effects on whole-animal thyroid hormone levels in larval and juvenile striped bass, Morone saxatilis. Fish Physiology and Biochemistry 8,507-514. 

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). 

L-thyroxine (T j or tetraiodo-L-thyronine) and liothyronine (Tg or triiodo-L-thyronine) are the natural hormones of the thyroid gland. is a less active precursor of Tj, which is the major mediator of physiological effect. In this chapter for therapeutic use is referred to as levothyroxine (the rINN, see p. 83) rather than levothyroxine (the former usage). 

Type III deiodinase catalyzes the conversion of T4 to reverse T3, and the conversion of T3 to T2- These steps constitute 5 -deiodination reactions. The enzyme occurs in the brain and skin of rats. The physiological role of the type III enzyme is thought to be to protect the brain from possible toxic effects of active thyroid hormone (T3). The placenta is distinguished in that it contains both type II and type III deiodinases (Glinoer, 1997). 

Steroid hormones (as well as the thyroid hormones, 1,25-dihydroxycholecalciferol, and retinoic acid cross) the cell membrane and bind to intracellular receptors. Ultimately, the hormone-receptor complex binds to DNA and activates or inactivates genes, which produce proteins that have physiologic effects. 

Thyroid hormone has multiple effects on the cardiovascular system with various physiological consequences. Several genes that encode important regulatory and structural proteins in the heart have been shown to be thyroid hormone responsive. Thyroid hormone increases cardiac contractility, induces vasorelaxation and angiogenesis, prevents fibrosis and has favorable effects on lipid metabolism (reviewed by Pantos73). 

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). 

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. 

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