{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,7,12]],"date-time":"2024-07-12T07:10:21Z","timestamp":1720768221349},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2006,12,18]],"date-time":"2006-12-18T00:00:00Z","timestamp":1166400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2007,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Background and objective\u2002<\/jats:bold> 1,25\u2010dihydroxyvitamin D<jats:sub>3<\/jats:sub>[1\u03b1,25(OH)<jats:sub>2<\/jats:sub>D<jats:sub>3<\/jats:sub>, calcitriol], and its less calcaemic synthetic analogues have therapeutic potential in several diseases, including hyperparathyroidism (HPT). We have suggested that non\u20101\u03b1\u2010hydroxylated (nonactive) vitamin D analogues may present an alternative in tumour cells expressing 25\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub> 1\u03b1\u2010hydroxylase (1\u03b1\u2010hydroxylase). The aim of this study was to investigate biological effects of a non\u20101\u03b1\u2010hydroxylated vitamin D analogue in normal and tumour parathyroid cells.<\/jats:p><jats:p><jats:bold>Patients and methods\u2002<\/jats:bold> Effects of vitamin D analogues and ketoconazole on parathyroid hormone (PTH) secretion (radioimmunoassay) and PTH mRNA expression (reverse transcription\u2010polymerase chain reaction) were studied in primary bovine parathyroid cells. Proliferation of tumour cells isolated from HPT patients was determined by thymidine incorporation<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> EB1285, non\u20101\u03b1\u2010hydroxylated precursor of the vitamin D analogue EB1089, suppressed PTH secretion and PTH mRNA level as well as increased expression of 25\u2010hydroxyvitamin D<jats:sub>3<\/jats:sub>\u201024\u2010hydroxylase (24\u2010hydroxylase) in bovine parathyroid cells. EB1285 also inhibited cell proliferation of parathyroid tumour cells from primary (pHPT) and secondary HPT (sHPT) patients. Combined treatment with the cytochrome P450\u2010dependent enzyme inhibitor ketoconazole and EB1285 or with active vitamin D compounds potentiated the suppressive effect on PTH secretion from bovine parathyroid cells. Ketaconazole alone displayed PTH suppression and increased 24\u2010hydroxylase expression.<\/jats:p><jats:p><jats:bold>Conclusion\u2002<\/jats:bold> The results support the idea that a non\u20101\u03b1\u2010hydroxylated vitamin D analogue may elicit vitamin D receptor (VDR) effects in 1\u03b1\u2010hydroxylase expressing parathyroid tumour cells. Further studies are warranted to elucidate whether precursor vitamin D analogues as well as inhibitors of 24\u2010hydroxylase present therapeutic alternatives in patients suffering from HPT.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2006.02746.x","type":"journal-article","created":{"date-parts":[[2006,12,20]],"date-time":"2006-12-20T10:54:19Z","timestamp":1166612059000},"page":"399-404","source":"Crossref","is-referenced-by-count":10,"title":["Potentiating effects of nonactive\/active vitamin D analogues and ketoconazole in parathyroid 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