title: Novel regulators of vitamin D action and metabolism: Lessons learned at the Los Angeles zoo.
abstract: We undertook an investigation of an outbreak of rachitic bone disease in the Emperor Tamarin New World primate colony at the Los Angeles Zoo in the mid-1980s. The disease phenotype resembled that observed in humans with an inactivating mutation of the vitamin D receptor (VDR), hypocalcemia, high 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) levels, and rickets in rapidly growing adolescent primates. In contrast to the human disease, the New World primate VDR was functionally normal in all respects. The proximate cause of vitamin D hormone resistance in New World primates was determined to be the constitutive overexpression of a heterogeneous nuclear ribonucleoprotein in the A family which we coined the vitamin D response element binding protein (VDRE-BP). VDRE-BP competed in trans with the VDR-retinoid X receptor (RXR) for binding to the vitamin D response element. VDRE-BP-legislated resistance to 1,25-(OH)(2)D was antagonized (i.e., compensated) by another set of constitutively overexpressed proteins, the hsp-70-related intracellular vitamin D binding proteins (IDBPs). IDBPs, present but expressed at much lower levels in Old World primates including man, exhibited a high capacity for 25-hydroxylated vitamin D metabolites and functioned to traffic vitamin Ds to specific intracellular destinations to promote their action and metabolism.
authors.affiliation: Burns and Allen Research Institute, Division of Endocrinology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, California, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Adams
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: R F
authors.initials: RF
authors.lastname: Chun
authors.forename: L
authors.initials: L
authors.lastname: Nguyen
authors.forename: S
authors.initials: S
authors.lastname: Wu
authors.forename: S Y
authors.initials: SY
authors.lastname: Ren
authors.forename: J
authors.initials: J
authors.lastname: Barsony
authors.forename: M A
authors.initials: MA
authors.lastname: Gacad
mesh_terms: D000818:Animals; D004351:Drug Resistance; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006370:Heliotherapy; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008992:Monkey Diseases / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D047488:Retinoid X Receptors; D012279:Rickets / Q000097:blood / Q000235:genetics* / Q000503:physiopathology* / Q000628:therapy; D012452:Saguinus / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D030181:Vitamin D Response Element / Q000502:physiology; D014809:Vitamin D-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D