Vitamin D in normal and pathological parathyroid glands: New prospects for treating hyperparathyroidism (Review)

The secosteroid hormone active vitamin D [1,25(OH)(2)D-3] is a key player in the regulation of calcium homeostasis and bone mineralization. In addition, it has antiproliferative and prodifferentiating effects on various cells in vitro and in vivo. The action of 1,25(OH)(2)D-3 is mediated through the vitamin D receptor (VDR), which belongs to the superfamily of steroid/thyroid hormone nuclear receptors. VDR is expressed in the intestine, bone, kidney, parathyroid glands, and in many other tissues and cell types. In the parathyroid glands, 1,25(OH)(2)D-3 markedly decreases parathyroid hormone gene transcription and parathyroid cell proliferation and induces parathyroid cell differentiation. Diminished VDR expression is frequent in parathyroid tumors and probably contributes to parathyroid tumorigenesis. The enzyme responsible for catalyzing synthesis of 1,25(OH)(2)D-3 (1 alpha-hydroxylase) has lately been demonstrated in the parathyroid glands. This indicates a new role for 1 alpha-hydroxylase as an intracrine modulator of vitamin D function in non-renal tissues, which recently has been recognized as crucial in parathyroid tumor development. The growth-inhibitory properties of 1,25(OH)(2)D-3 are prospects for treatment of hyperparathyroidism.