Vitamin thyroid hormones

Figure 10.12 Response elements for heterodimers of the nuclear receptor for ds-retinoic acid (RXR) with the receptors for vitamin D (VDR), thyroid hormone (TR) and trans-retinoic acid (RAR). The half-sites of these response elements have identical nucleotide sequences and are organized as direct repeats. They differ in the number of base pairs in the spacer region between the half-sites. This difference forms the basis for the ability of the heterodimers to discriminate between the different response elements.

Brouwer, A. (1991). Role of biotransformation in PCB-induced alterations in vitamin A and thyroid hormone metabolism in laboratory and wildlife species. Biochemical Society Transactions 19, 731-737. 

Signals that enter the cell (steroids, vitamin D, thyroid hormone, and retinoids)... 

The signal is what starts everything off. Signals take a variety of forms, but for our purposes there are only two. The first type are signals that go into the cell, bind to internal receptors, and exert their effects. Steroid hormones, vitamin D, thyroid hormone, and retinoids are the only members of this class. All of the intracellular receptors ultimately activate the transcription of regulated genes. The common feature of signals that enter the cell is that they are all small lipophilic molecules that can cross the cell membrane. 

The signal crosses the membrane and activates gene transcription. Signals for soluble receptors include steroid hormones, retinoic acid, thyroid hormone, and vitamin D. 

Transport of thyroid hormones Transport of vitamin A Osmotic regulation of plasma Non-specific carrier... 

Iodine is essential in the mammalian diet to produce the thyroid hormone thyroxine deficiency in humans causes goitre. Collectively, deficiencies of iodine, iron, zinc and vitamin A in humans are thought to be at least as widespread and debilitating as calorie deficiencies (Welch and Graham, 1999). The main source of iodine in soils is oceanic salts rather than parent rock, and so deficiency is most widespread in areas remote from the sea (Fuge, 1996). In principle deficiency is easily corrected with dairy supplements. However in practice this is not always feasible. Addition of iodate to irrigation water has successfully corrected widespread iodine deficiency in parts of China where the usual methods of supplementation had failed (Cao et al., 1994 Jiang et al 1997). However there is not much information on the behaviour of iodine in soil and water systems. 

The superfamily of nuclear receptors includes about 150 proteins in the human genome. These are the targets of all principal classes of steroids as well as those of retinoids, vitamin D, and thyroid hormones. 

Enzyme induction properties Rifampin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones, and vitamin D. Rifampin and isoniazid have been reported to alter vitamin D metabolism. In some cases, reduced levels of circulating 25-hydroxy vitamin D and 1,25-dihydroxy vitamin D have been accompanied by reduced serum calcium and phosphate, and elevated parathyroid hormone. 

This mechanism is used by steroid hormones (Table 14—2), thyroid hormone, vitamin D3, and retinoic acid. 

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. 

---