Reduced parathyroid vitamin D receptor messenger ribonucleic acid levels in primary and secondary hyperparathyroidism

Vitamin D, via its receptor (VDR), inhibits the hormone secretion and proli feration of parathyroid cells. Vitamin D deficiency and reduced parathyroid VDR expression has been associated with development of hyperparathyroidism (HPT) secondary to uremia. VDR polymorphisms may influence VDR messenger R NA (mRNA) levels and have been coupled to an increased risk of parathyroid adenoma of primary HPT. VDR mRNA relative to glyceraldehyde-3-phosphate deh ydrogenase mRNA levels were determined by RNase protection assay in 42 sing le parathyroid adenomas of patients with primary HPT, 23 hyperplastic gland s of eight patients with uremic HPT, and 15 normal human parathyroid glands . The adenomas and hyperplasias demonstrated similar VDR mRNA levels, which were reduced (42 +/- 2.8% and 44 +/- 4.0%) compared with the normal glands (P < 0.0001). Comparison of parathyroid adenoma with a normal-sized parath yroid gland of the same individual (n = 3 pairs) showed a 20-58% reduction in the tumor. Nodularly enlarged glands represent a more advanced form of s econdary HPT and showed greater reduction in the VDR mRNA levels than the d iffusely enlarged glands (P < 0.005). The reduced VDR expression is likely to impair the 1,25(OH)(2)D-3-mediated control of parathyroid functions, and to be of importance for the pathogenesis of not only uremic but also prima ry HPT. Circulating factors like calcium, PTH, and 1,25(OH)(2)D-3 seem to b e less likely candidates mediating the decreased VDR gene expression in HPT .