Retinoic acid receptors and interaction with vitamin D and thyroid hormone signaling
THE CONTEXT
Vitamin A regulates cell differentiation and turnover. Its retinoic acid forms control gene transcription through nuclear receptors.
Regulation of gene expression
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All-trans-retinoic acid and 9-cis-retinoic acid regulate growth, development, and tissue differentiation, with different actions in different tissues.
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Retinoic acid binds nuclear receptors that bind DNA response elements and regulate transcription of specific genes.
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Retinoic acid receptors, abbreviated RAR, bind either all-trans-retinoic acid or 9-cis-retinoic acid.
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Retinoid X receptors, abbreviated RXR, bind 9-cis-retinoic acid and form dimers with vitamin D, thyroid, and other nuclear acting hormone receptors.
Effects of vitamin A deficiency
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Vitamin A deficiency reduces the availability of 9-cis-retinoic acid needed for active receptor dimers, impairing vitamin D and thyroid hormone function.
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Unoccupied RXRs can still form dimers with occupied vitamin D and thyroid hormone receptors.
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These dimers fail to activate gene expression and may repress it, making the effect more severe than a simple failure of gene activation.
Effects of vitamin A excess
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Excessive vitamin A also impairs vitamin D and thyroid hormone function.
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RXR homodimer formation leaves too few RXRs available to form heterodimers with vitamin D and thyroid hormone receptors.