25-hydroxyvitamin D3-1α-hydroxylase expression in normal and pathological parathyroid glands

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 D3-1α-hydroxylase (1α-hydroxylase), which is potently induced by PTH. However, 1α-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 1α -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 1α-hydroxylase in normal and pathological parathyroid tissue. With real-time quantitative RT-PCR a...