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Active vitamin D, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], plays a pivotal role in calcium homeostasis and bone metabolism. Circulating levels of 1,25(OH)2D3 are thought to be dependent mainly on the activity of the renal cytochrome P450 enzyme 25-hydroxyvitamin D3-1[alpha]-hydroxylase (1[alpha]-hydroxylase), which is potently induced by PTH. However, 1[alpha]-hydroxylase activity or expression has also been reported at several extrarenal sites, at which local synthesis of 1,25(OH)2D3 appears to fulfill autocrine or paracrine functions. This includes tissues such as placenta and brain that also express LRP-2/megalin, an endocytic receptor for multiple ligands, which is involved in the renal uptake of the substrate for 1[alpha] -hydroxylase, 25-hydroxyvitamin D3. We have previously demonstrated LRP-2/megalin in parathyroid cells, and here we present results from RT-PCR and immunohistochemical analyses showing coincident expression of 1[alpha]-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression of 1[alpha]-hydroxylase mRNA was higher in the majority of parathyroid adenomas and secondary hyperplastic glands but lower in parathyroid carcinomas, compared with normal parathyroid tissue. The findings imply that in addition to feedback control by circulating 1,25(OH)2D3 levels, parathyroid cells may also be influenced by local 1[alpha] -hydroxylase activity with possible growth regulatory and differentiating effects.

Copyright (C) 2002 by The Endocrine Society