Vitamin D receptors in a naturally vitamin D-deficient subterranean mammal, the naked mole rat (Heterocephalus glaber): biochemical characterization.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3), the hormonally active metabolite of vitamin D3 interacts with its nuclear/cytosolic receptor to induce biological responses in target tissues. Naked mole rats appear to be naturally deficient in vitamin D. The questions arise whether these animals possess the 1,25(OH)2D3 receptor (VDR) and whether they are capable of responding to 1,25(OH)2D3 via receptor-mediated pathways. Various tissues (intestine, kidney, Harderian glands, and skin) were examined for the presence and biochemical characterization (as indicated by saturation, sucrose density gradient, DNA binding, and ligand-competitive analysis) of VDRs. In addition homologous upregulation of VDRs in these tissues and induction of 25-hydroxyvitamin D3-24-hydroxylase (24-OHase) in the kidney was studied as indicators of the VDR-mediated biological responses. Naked mole rats have VDRs in the intestine, kidney, and Harderian gland but not in skin. Biochemical characterization of VDRs and VDR-mediated biological responses in the intestine and kidney correspond to those found in similar target tissues of other mammals. Harderian gland VDR is at a lower concentration yet shows a markedly higher affinity and selectivity to 1,25(OH)2D3 than that of the intestine and kidney. Vitamin D3 supplementation resulted in VDR upregulation in the intestine and kidney and induced renal 24-OHase but had no effects on VDRs in Harderian glands. These data demonstrate that naked mole rats possess VDRs in intestine, kidney, and Harderian glands; these VDRs differ in their biochemical characteristics.
Sergeev
I N
IN
Department of Paediatrics, Medical School, University of the Witwatersrand, Johannesburg, South Africa.
Buffenstein
R
R
Pettifor
J M
JM
D000818:Animals; D002499:Centrifugation, Density Gradient; D002845:Chromatography; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005260:Female; D006243:Harderian Gland / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000737:chemistry / Q000648:ultrastructure; D007668:Kidney / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D008024:Ligands; D008297:Male; D018167:Receptors, Calcitriol / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012377:Rodentia / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D013250:Steroid Hydroxylases / Q000032:analysis / Q000378:metabolism; D015854:Up-Regulation; D014807:Vitamin D / Q000378:metabolism / Q000494:pharmacology; D014808:Vitamin D Deficiency / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D008024:Ligands; D018167:Receptors, Calcitriol; D014807:Vitamin D; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase