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Hair Loss Study Abstract: Vitamin B6 modulates transcriptional activation by multiple members of the steroid hormone receptor superfamily.
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Title
Vitamin B6 modulates transcriptional activation by multiple members of the steroid
hormone receptor superfamily.
Author
Allgood VE; Cidlowski JA
Address
Department of Physiology, University of North Carolina, Chapel Hill 27599-7545.
Source
J Biol Chem, 267(6):3819-24 1992 Feb 25
Abstract
Recent studies have shown that vitamin B6 modulates transcriptional activation by the
human glucocorticoid receptor in HeLa S3 cells. We have now examined the possibility that
vitamin B6 might similarly influence transcriptional activation by the glucocorticoid
receptor in other cell types, as well as gene expression mediated by other members of the
steroid hormone receptor superfamily. We show that elevated vitamin B6 concentrations
suppress by 40-65% the level of transcription mediated through the endogenous murine L
cell glucocorticoid receptor, as well as the human receptor transfected into E8.2 and T47D
cells. In contrast, glucocorticoid receptor-mediated transcription was enhanced 60-110% in
mild vitamin deficiency. The level of hormone-independent constitutive gene expression was
not affected by these same alterations in vitamin B6 concentration. These studies
indicated that the transcriptional modulatory effects of the vitamin were neither
restricted to specific cell types nor limited to the human form of the glucocorticoid
receptor. We next determined if hormone-induced transcription by several other steroid
receptors (androgen, progesterone, and estrogen receptors) was analogously affected by
alterations in vitamin B6 concentration. Analysis of gene expression mediated through the
mouse mammary tumor virus promoter revealed that transcriptional activation of both the
androgen and progesterone receptors was reduced by 35-40% under conditions of elevated
vitamin B6 and enhanced by 60-90% in deficiency, again under conditions where constitutive
expression was unaffected. Using a different promoter, the estrogen-regulated vitellogenin
promoter, we found that transcriptional activation of the estrogen receptor was similarly
affected. Estrogen-induced gene expression was reduced by 30% under conditions of elevated
intracellular vitamin B6 and enhanced by 85% in vitamin deficiency. Thus, vitamin B6
modulates transcriptional activation by multiple classes of steroid hormone receptors. The
similarities in vitamin B6 effects on transcription mediated through different promoters,
the mouse mammary tumor virus and vitellogenin promoters, suggest that this vitamin may
modulate the expression of a diverse array of hormonally responsive genes. These
observations together support the hypothesis that vitamin B6 represents a physiological
modulator of steroid hormone action.
Language
Eng
Unique Identifier
92156119
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