Thyroid hormones possible mechanism

Brouwer, A., Morse, D.C., and Lans, M.C. et al. (1998). Interactions of persistent enviromnen-tal organohalogens with the thyroid hormone system Mechanisms and possible conse-qnences for animal and hnman health. Toxicology and Industrial Health 14, 59-84. 

Brouwer A, Morse DC, Lans MC, SchuurAG, MurkAJ, Klasson-Wehler E, Bergman A, Visser TJ (1998) Interactions of persistent environmental organohalogens with the thyroid hormone system Mechanisms and possible consequences for animal and human health. Toxicol Ind Health, 14 59-84. 

THYROID HORMONES QUINOLONES -CIPROFLOXACIN i levels of levothyroxine and possible therapeutic failure The mechanism has not been elucidated the concurrent administration of ciprofloxacin with levothyroxine may interfere with the absorption of levothyroxine and result in lower than expected levels The interaction may be minimized by separating dosing of the two agents ciprofloxacin should be taken several hours before or after taking levothyroxine... 

Although this literature has been reviewed extensively16,36,47 54-56 65 it is still not understood precisely how the fish thyroid system responds to any given xenobiotic and what the biological consequences might be. In light of this we have focused on possible mechanisms of fish thyroid disruption. We have commenced with brief overviews of the properties of thyroid hormones (TH) and the thyroid cascade and have then considered the problems inherent in evaluating fish thyroidal responses. 

Figure 57.4 The possible link between thyroid hormone synthesis, oxidative stress and mutagenesis in the thyroid gland. This figure illustrates the mechanism, the sequence of steps and the key moleoules that link thyroid hormone synthesis, iodine deficiency, oxidative stress, DNA damage and possible mutagenesis. ThOX, thyroid oxidase TPO, thyroid peroxidase T3, T4, thyroid hormones.

Previously published reports have described both sub-clinical and overt thyroid dysfunction as a result of excess iodine ingestion. Moreover, iodine-induced hypothyroidism is not rare, at least in iodine-replete areas. The possible underlying mechanisms of this impairment consist of both the inhibition of thyroid function by excess iodine and the iodine-induced enhancement of thyroid autoimmunity. On the basis that an excess iodine intake may cause hypothyroidism, several study results support iodine restriction for the treatment of hypothyroidism. The success rate of dietary iodine restriction alone, without thyroid hormone replacement, is reported to be approximately 50-80% in patients with primary hypothyroidism due to Hashimotos thyroiditis and other causes. Relatively mild hypothyroidism, high radioactive iodine uptake and uptake, increased free plasma iodine and... 

The proposition that the mechanism of action of thyroid hormones is the same as that of DNP is untenable on physiological grounds, for while DNP can raise the BMR of a myxedematous patient to normal, the other symptoms of myxedema are unrelieved (cf. Pitt-Rivers and Tata, 1959). An uncoupling of oxidative phosphorylation secondary to some other and more general action of thyroxine is, however, possible such a decreased phos-phorylating ability has, in fact, been demonstrated with mitochondria from thyrotoxic rats (Niemeyer et al., 1951 Lardy and Feldott, 1951 ... 

Finally, and since only one Tau gene hcis been detected (29,39) it might be that the juvenile and adult Tau proteins are generated a splicing mechanism. If this possibility is confirmed an important question will be to know how such a mechanism is regulated to account for the sharp differential expression between juvenile and mature Tau which is observed dur g hredn development. Such an information is probably also essential to understand hew thyroid hormones modify the expression of these proteins. 

There are a number of possibilities that could account for the interaction between thyroid hormone and NGF. For example, treatments with insulin and insulin-like growth factor II have been found to increase specific and saturable NGF binding sites in cultured human neuroblastoma cells.It is possible that analogous mechanisms between thyroid hormone and NGF may operate in subcortical cholinergic cells. Another possibility could be that if thyroid hormone controls the formation of ChAT or of proteins essential for cholinergic cell maturation at a pretranslational level S and NGF regulates the de novo synthesis of these crucial proteins at transcriptional level,30 then a combination of these effects could synergistically potentiate ChAT activity. 

Ontogenetic features of thyroid hormone processing in brain have been characterized on the basis of new morphologic, biochemical and functional evidence. This evidence raises the possibility that, like other neuroactive substances, thyroxine may participate in developmental events through a series of separate but related mechanisms. 

In summary, thyrotropin secretion is feedback regulated by circulating levels of T3 and possibly T4. Increased levels of these compounds in the blood result in a decreased level of thyrotropin. The thyroid hormones block the action of TRH on the pituicyte by stimulating the formation of a protein which masks the effect for TRH without interfering with the elaboration of TSH. The molecular mechanism by which the newly synthesized protein interferes with TRH activity is not known. 

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