A, Vitamin D, and Thyroid Hormone at the Genome

Vitamin D has recently found an association with psoriasis, a common disease of the skin. Psoriasis is not curable, but a variety of skin ointments can reduce the severity of the skin lesions. One of these ointments is a chemical analogue of vitamin D called calcipotrlene. Calcipotrienc was developed after initial observations that oral or topical caldtriol was effective against the disease, The drug results in improvement tn 60% of patients (Greaves and Weinstein, 1995), 

3- The heterodimer bind.s tightly to the regulatory sequence of DNA, The regulatory sequence containing the pair of GGGTCA sequences is called the hormone respo sc element. The half-core sequences that bind to the RXR / RAR complex, for example, are separated by four nucleotides, where the exact identity t f these nucleotides is usually not vital to the functioning of the 

TABLE 9.7 List of Ligands, Transcription Factors, and Hormone Binding Elements 

Ligand TranMTipticin factor 1 (orniDne binding element (both strands of DNA aie shown) 

Prostaglandin (proposed ligand) PPAR/RXR OGfiTCAHGCCTCA CCCXGTNCCC. C-T 

The ligand binds to RAR (or PPAR, THR, or VDR) to form a ligand/protein complex. 

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A, Vitamin D, and Thyroid Hormone at the Genome, and in the Essential Fatty Acid section. 

Maximal expression of the nuclear effects of the vitamin requires an hour or so after exposure of the cell to l,25-(OH)2D3. The l,25-(OH)2D3 entering the cell binds to VDR to form a hormone/receptor complex. The hormone/receptor complex binds to small stretches of DNA called hormone response elements and provokes a change in the rate of transcription of a nearby gene. The term "nearby" means that the hormone response element and the gene may be separated from each other by a stretch of from 20 to 1000 nucleotides away from each other. Further details on the nuclear action of vitamin D occur in the section entitled Vitamin A, Vitamin D, and Thyroid Hormone at the Genome. 

Changes in thyroid hormone levels in the body provoke consequent changes in metabolism by forming a complex with a special transcription factor, the thyroid hormone receptor. The hormone/receptor complex then binds to special regions of the chromosome and provoke changes in the rate of transcription of nearby genes. Details of this scenario were presented in the vitamin chapter in the section on Vitamin A, Vitamin D, and Thyroid Hormone at the Genome. 

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