Production of 1,25-dihydroxyvitamin D3 by human T cell lymphotrophic virus-I-transformed lymphocytes.
The human T cell lymphotrophic virus type I (HTLV-I) has recently been identified in a T cell lymphoma associated with hypercalcemia and increased bone turnover. Since increased serum concentrations of 1,25-dihydroxyvitamin D have been reported in this disease, we have examined the capacity of HTLV-I-infected cord blood lymphocytes to metabolize 25-hydroxyvitamin D3. Our results demonstrate that HTLV-I-infected cells have the capacity to metabolize 25-hydroxyvitamin D3 to a substance that co-migrates with 1,25-dihydroxyvitamin D3 by high performance liquid chromatography over a silica column using either 12% isopropanol in hexane or 5% isopropanol in dichloromethane. The metabolite binds to the 1,25-dihydroxyvitamin D3 receptor in rat osteosarcoma cells and stimulates bone resorption in cultures of fetal rat long bones. Mass spectrometric analysis of the metabolite confirmed the presence of 1,25-dihydroxyvitamin D3. Production of 1,25-dihydroxyvitamin D by lymphoma cells may contribute to the pathogenesis of the hypercalcemia seen in patients with HTLV-I-associated T cell lymphomas.
D000818:Animals; D002117:Calcitriol / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology; D002460:Cell Line; D002472:Cell Transformation, Viral; D017977:Deltaretrovirus / Q000502:physiology*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008213:Lymphocyte Activation; D012516:Osteosarcoma / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism*
D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D002117:Calcitriol