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25-Hydroxyvitamin D₃-1-Hydroxylase Expression in Normal and Pathological Parathyroid Glands

Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, SE-751 85 Uppsala, Sweden

Address all correspondence and requests for reprints to: Gunnar Westin, Ph.D., Department of Surgical Sciences, Endocrine Unit, Uppsala University Hospital, Klinisk forskningsavdelning 2, ingang 70, plan 3, lab 9, SE-751 85 Uppsala, Sweden. E-mail: . gunnar.westin{at}surgsci.uu.se

Abstract

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-hydroxylase (1-hydroxylase), which is potently induced by PTH. However, 1-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 -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-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR analysis, the expression of 1-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 -hydroxylase activity with possible growth regulatory and differentiating effects.

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