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.