MODULATION OF STEROID RECEPTOR-MEDIATED GENE-EXPRESSION BY VITAMIN-B-6

Gene transcription mediated by steroid hormones has become one of the most extensively characterized model systems for studying the regulati on of gene expression in eukaryotic cells. However, specific details o f gene regulation by steroid hormones are often complex and may be uni que in specific cell types. Diverse regulatory mechanisms leading to e ither activation or repression of particular genes frequently involve interactions between steroid hormone receptors and other ubiquitous an d/or cell-specific transcription factors that act on the complex promo ter of the regulated gene. Interplay between steroid receptor-mediated and other signal transduction pathways may also be involved. In addit ion, recent novel results indicate that moderate variations in the int racellular concentration of pyridoxal 5'-phosphate (PLP), the biologic ally active form of vitamin B-6, can have pronounced modulatory effect s on steroid-induced gene expression. Specifically, elevation of intra cellular PLP levels leads to decreased transcriptional responses to gl ucocorticoid, progesterone, androgen, or estrogen hormones. Conversely , cells in a vitamin B-6-deficient state exhibit enhanced responsivene ss to steroid hormones. One aspect of the mechanism by which these tra nscriptional modulatory effects of PLP occur has recently been shown t o involve interruption of functional interactions between steroid horm one receptors and the nuclear transcription factor NF1. These findings -that the vitamin B-6 nutritional status of cells modulates their capa city to respond to steroid hormones-impose an additional level of cell -specitic control over steroid hormone regulation of gene expression a nd will serve as the focal point for this review.