Thyroxine, synthesis

Isoflavones have been implicated in goiter induction. Soybean extracts inhibit reactions catalyzed by thyroid peroxidase (TPO), essential to the synthesis of thyroid hormones (Divi et al., 1997). Genistein and daidzein (at about 1-10 p,M of IC50) may act as alternative substrates for tyrosine iodination (Divi et al., 1997). Furthermore, genistein and daidzein have also been shown to cause the irreversible inactivation of TPO in the presence of hydrogen peroxide. Genistein also inhibits thyroxine synthesis in the presence of iodinated... 

Thyroxine synthesis begins when iodide (I-) is transferred from the blood stream to the thyroid follicle cell by an active ATP-driven membrane pump mechanism this process is stimulated by cAMP following TSH stimulation of the gland. Iodide is transported through the follicular cell and secreted into the lumen of the follicle where it is oxidized to iodine and incorporated in to tyrosine residues by the enzyme thyroid peroxidase (TPO). 

This drug has a pronounced thyrostatic effect and canses reduced thyroxine synthesis in the thyroid gland. It inhibits the process of iodination of thyroglobnUn, reduces formation of the active form of iodine in the thyroid gland, and blocks the peroxidase system. Propylthionracil is nsed for hyperthyrosis, thyrotoxic crises, and on thyrodectomia. Synonyms of this dmg are propycil and tireostat. 

It also inhibits ADH action on distal tubules (diabetes insipidus like state), also has insulin like action on glucose metabolism and decreases thyroxine synthesis by interfering with iodination of thyroxine. 

Lithium affects thyroid function (52-56), and in most patients, after 4 months of treatment, there is a transient fall in serum levels of thyroxine (T4) and a rise in thyrotropic hormone (thyroid-stimulating hormone, TSH). After 1 year of treatment, these hormones have generally returned to their baseline. The mechanisms for this are obscure, but lithium inhibits both thyroxine synthesis and its release from the gland (201). Lithium may inhibit endocytosis in the thyroid gland, which results in an accumulation of colloid and thyroglobulin within the follicles, thereby reducing hormone release (202). Thyroid volume... 

FIGURE 56-5 Regulation of thyroid hormone secretion. Myriad neural inputs influence hypothalamic secretion of thyrotropin-releasing hormone (TRH). TRH stimulates release of thyrotropin (TSH, thyroid-stimulating hormone) from the anterior pituitary TSH stimulates the synthesis and release of the thyroid hormones and T,. and T, feed back to inhibit the synthesis and release of TRH and TSH. Somatostatin (SST) can inhibit TRH action, as can dopamine and high concentrations of glucocorticoids. Low levels of L are required for thyroxine synthesis, but high levels inhibit thyroxine synthesis and release. 

After the initiation of fetal thyroxine synthesis, transfer of thyroid hormones from the mother to the fetus does not stop, but continues until birth. During that period, 20—50% of cord serum thyroxine is composed from maternal supply (de Escobar et aL, 1990 Vulsma et ai, 1989). Several clinical syndromes attributable to iodine deficiency vary according to the timing and the severity of the deficiency. It has been shown that neurodevelopmental disorders in... 

The coupling reaction may be either intermolecular, as for a synthesis of an intermediate in a synthesis of thyroxine 2.605 (Scheme 2.179), or intramolecular, as in a synthesis of a metalloproteinase inhibitor 2.607 (Scheme 2.180) (for a different approach to related peptides, see Scheme 10.47). It is notable in the thyroxine synthesis that the two iodine substituents of coupling substrate 2.602 are not affected and no Suzuki products are formed in the absence of palladium. 

Oxazolidine-2-thiones (e.g. progoitrin see Figure 7.20) inhibit thyroxine synthesis by inhibition of iodination of monoiodotyrosine to di-iodotyrosine. They are goitrogenic regardless of iodine nutritional status. 

Several theoretical schemes to explain the mechanism of thyroxine synthesis have been proposed. These are reviewed by Harington 274) and by Neuberger 276). 

Hormones are supposed to act only on specific tissues or cells which are called target tissues or target cells. The specificity of hormonal action is expressed at two levels (1) hormone-tissue interaction, and (2) cell reaction to hormonal stimulus. In the target cells, the hormones interact with specific structures— the receptors. The degree of specificity of the receptors conditions the specificity of the interaction. As the receptor for lipolytic hormones in the fat cell reacts with several hormones, so does the fat cell. All cells containing /7-receptors for adrenaline will respond to this hormone. The reaction of a tissue to a hormonal stimulus depends on the metabolic and structural characteristics of this tissue. Thyrotropin activates lipo-lysis in the fat cell, thyroxine synthesis in the thyroid, and insulin secretion by the pancreatic /7-celL... 

Certain substances (such as anetholtrithion, phenylthiocarbamide and other related thiourea derivatives) which are perceived as bitter by the great majority of human populations are tasteless for a minority. This factor is genetically controlled. A higher percentage of goiter is foimd in the population of non-tasters , but it is not known whether the metabolic effects of thioiu ea (inhibition of thyroxine synthesis) is different in tasters and non-tasters. 

Antithyroid Substances. Various substances are able to interfere with the normal process of thyroxine synthesis. First of all, several univalent anions (e.g. thio-... 

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