Vitamin B6 Modulation of Steroid Receptor-mediated Gene Expression

Douglas B Tully,John A Cidlowski,Alyson B Scoltock

doi:10.1007/978-3-0348-7393-2_51

Douglas B Tully, John A Cidlowski + Show 1 more

https://doi.org/10.1007/978-3-0348-7393-2_51

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SummarySteroid hormones regulate many physiological processes in tissues and cell types throughout the body, including such fundamental biological processes as growth, development, reproduction, regulation of metabolic state, and maintenance of homeostasis. Steroid hormones elicit their biological effects at the single cell level by regulating the expression of distinct target genes. Each type of steroid hormone binds specifically to a unique intracellular receptor protein, and this binding initiates transformation of the receptor into a form which is capable of selective interaction with DNA regulatory sequences that typically reside within or near the promoter regions of hormone-responsive genes. Interactions of the steroid-receptor complex with these DNA regulatory sites results in modulation of target gene expression that ultimately alters the phenotype of steroid-responsive cells Because steroid receptors are critically involved in so many biological processes, there has been considerable interest in determining both the mechanisms through which steroid hormone action is mediated and related regulatory mechanisms which control the degree of cellular responsiveness to steroid hormones. We have recently shown that vitamin B6 modulates transcriptional activation of gene expression by glucocorticoid, progesterone, estrogen and androgen receptors in a variety of cell lines. In each case elevated intracellular pyridoxal phosphate concentrations inhibit steroid responses, whereas vitamin B6 deficiency enhances cellular responses to steroid administration. We have further shown that modulation of receptor-mediated gene expression by vitamin B6 occurs only on complex promoters containing a binding site for Nuclear Factor 1 in addition to the appropriate steroid hormone response element. This new finding suggests that pyridoxal phosphate modulates the ability of steroid receptors to communicate with other transcription factors.

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