科研之友
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摘要
Parathyroid glands express the 25-hydroxyvitamin D-3 1 alpha-hydroxylase (1 alpha OHase). 1,25-dihydroxyvitamin D-3 (calcitriol) synthesized by extrarenal tissues generally does not enter the circulation, but plays an autocrine/paracrine role specific to the cell type, and is regulated by the needs of that particular cell. While the role of calcitriol produced in the parathyroid glands presumably is to suppress PTH and cell growth, its regulation in this cell type has not been defined. In the present study, we found that regulation of the human parathyroid 1 alpha OHase differs from the renal enzyme in that it is induced by FGF-23 and extracellular calcium. Hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. We found that the 1 alpha OHase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. Recent findings indicate that oxyphil cell content is increased by treatment with calcium receptor activators (calcimimetics). Here, we demonstrate that the calcimimetic cinacalcet increases the expression of 1 alpha OHase in human parathyroid cultures. Additionally, we found that the 1 alpha OHase in human parathyroid cultures is functionally active, as evidenced by the ability of the enzyme to 1-hydroxylate 25(OH)D-3 in parathyroid monolayers. Calcium, as well as cinacalcet, also induced expression of the degradation enzyme 24-hydroxylase, indicating the presence of a negative feedback system in the parathyroid cells. Therefore, local production of 1 alpha OHase suggests an autocrine/paracrine role in regulating parathyroid function and may mediate, in part, the suppression of PTH by calcium and FGF-23.
- 出版日期2012-5
