Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth

G. Kerr Whitfield, Hope T.L. Dang, Samuel F. Schluter, Ralph M. Bernstein, Tara Bunag, Lori A. Manzon, Grace Hsieh, Carlos Encinas Dominguez, John H. Youson, Mark R. Haussler, John J. Marchalonis

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85 Scopus citations

Abstract

The nuclear vitamin D receptor (VDR) mediates the actions of its 1,25-dihydroxyvitamin D3 ligand to control gene expression in terrestrial vertebrates. Prominent functions of VDR-regulated genes are to promote intestinal absorption of calcium and phosphate for bone mineralization and to potentiate the hair cycle in mammals. We report the cloning of VDR from Petromyzon marinus, an unexpected finding because lampreys lack mineralized tissues and hair. Lamprey VDR (lampVDR) clones were obtained via RT-PCR from larval protospleen tissue and skin and mouth of juveniles. LampVDR expressed in transfected mammalian COS-7 cells bound 1,25-dihydroxyvitamin D3 with high affinity, and transactivated a reporter gene linked to a vitamin D-responsive element from the human CYP3A4 gene, which encodes a P450 enzyme involved in xenobiotic detoxification. In tests with other vitamin D responsive elements, such as that from the rat osteocalcin gene, lampVDR showed little or no activity. Phylogenetic comparisons with nuclear receptors from other vertebrates revealed that lampVDR is a basal member of the VDR grouping, also closely related to the pregnane X receptors and constitutive androstane receptors. We propose that, in this evolutionarily ancient vertebrate, VDR may function in part, like pregnane X receptors and constitutive androstane receptors, to induce P450 enzymes for xenobiotic detoxification.

Original languageEnglish (US)
Pages (from-to)2704-2716
Number of pages13
JournalEndocrinology
Volume144
Issue number6
DOIs
StatePublished - Jun 1 2003

ASJC Scopus subject areas

  • Endocrinology

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    Whitfield, G. K., Dang, H. T. L., Schluter, S. F., Bernstein, R. M., Bunag, T., Manzon, L. A., Hsieh, G., Dominguez, C. E., Youson, J. H., Haussler, M. R., & Marchalonis, J. J. (2003). Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth. Endocrinology, 144(6), 2704-2716. https://doi.org/10.1210/en.2002-221101