Thyroid mediated mechanisms

Thyroid hormone mechanisms of action can be classified into two types (1) genomic or nuclear and (2) nongenomic, including effects at the plasma membrane and mitochondria. Genomic effects involve modification of gene transcription, are mediated only by Tj, and require at least several hours to detect. Nongenomic actions are generally rapid in onset and occur in response to T4 and some T4 metabolites (e.g., rT3,T3, and Tj). 

Control of thyroid function via thyroid-pituitary feedback is also discussed in Chapter 37. Briefly, hypothalamic cells secrete thyrotropin-releasing hormone (TRH) (Figure 38-3). TRH is secreted into capillaries of the pituitary portal venous system, and in the pituitary gland, TRH stimulates the synthesis and release of thyrotropin (thyroid-stimulating hormoneTSH). TSH in turn stimulates an adenylyl cyclase-mediated mechanism in the thyroid cell to increase the synthesis and release of T4 and T3. These thyroid hormones act in a negative feedback fashion in the pituitary to block the action of TRH and in the hypothalamus to inhibit the synthesis and secretion of TRH. Other hormones or drugs may also affect the release of TRH or TSH. 

Changes in plasma corticosterone and thyroxine concentrations were reported in salamander larvae Ambystoma tigrinum) exposed to atrazine at concentrations of 75 and 250 g/L (29). The authors did not suggest that this was an atrazine-specific mechanism but rather that it was a conq>ensatory response to stress from an environmental contaminant. In addition, since die development of the laryngeal dilator muscle is dependent on both androgen and thyroid hormone, the fact that effects were not observed in male X, laevis in all but one of the studies conducted with atrazine supports the conclusion that atrazine did not disrupt thyroid hormone status in these frogs (17,19,27), Overall, there is no evidence that atrazine affects thyroid-mediated processes in amphibians. 

Liu R, Li Z, Bai S, et al. Mechanism of cancer cell adaptation to metabolic stress proteomics identification of a novel thyroid hormone-mediated gastric carcinogenic signaling pathway. Mol. Cell. Proteomics 2009 8 70-85. 

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. 

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