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

Research output: Contribution to journalArticle

78 Citations (Scopus)

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

Fingerprint

Petromyzon
Lampreys
Calcitriol Receptors
Skeleton
Vertebrates
Organism Cloning
Tooth
Calcitriol
Xenobiotics
Vitamin D
Hair
Cytochrome P-450 Enzyme System
Genes
Cytochrome P-450 CYP3A
Physiologic Calcification
COS Cells
Osteocalcin
Intestinal Absorption
Cytoplasmic and Nuclear Receptors
Reporter Genes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth. / Whitfield, G Kerr; Dang, Hope T L; Schluter, Samuel F.; Bernstein, Ralph M.; Bunag, Tara; Manzon, Lori A.; Hsieh, Grace; Dominguez, Carlos Encinas; Youson, John H.; Haussler, Mark R; Marchalonis, John J.

In: Endocrinology, Vol. 144, No. 6, 01.06.2003, p. 2704-2716.

Research output: Contribution to journalArticle

Whitfield, GK, Dang, HTL, Schluter, SF, Bernstein, RM, Bunag, T, Manzon, LA, Hsieh, G, Dominguez, CE, Youson, JH, Haussler, MR & Marchalonis, JJ 2003, 'Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth', Endocrinology, vol. 144, no. 6, pp. 2704-2716. https://doi.org/10.1210/en.2002-221101
Whitfield, G Kerr ; Dang, Hope T L ; Schluter, Samuel F. ; Bernstein, Ralph M. ; Bunag, Tara ; Manzon, Lori A. ; Hsieh, Grace ; Dominguez, Carlos Encinas ; Youson, John H. ; Haussler, Mark R ; Marchalonis, John J. / Cloning of a functional vitamin D receptor from the lamprey (Petromyzon marinus), an ancient vertebrate lacking a calcified skeleton and teeth. In: Endocrinology. 2003 ; Vol. 144, No. 6. pp. 2704-2716.
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