J. Martinez et al., 1,25-DIHYDROXYVITAMIN D-3 RECEPTORS IN PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH PRIMARY AND SECONDARY HYPERPARATHYROIDISM, Bone and mineral, 27(1), 1994, pp. 25-32
A decreased number of calcitriol (1,25(OH)(2)D-3) receptors has been o
bserved in parathyroid glands of uremic animals. In humans, studies ca
rried out in surgically removed parathyroid glands have shown that cal
citriol binding is higher in primary than in secondary hyperparathyroi
dism. Since specific receptors for calcitriol have been described in p
eripheral blood mononuclear cells (PBMC), we have investigated the spe
cific uptake of H-3-labelled 1,25(OH)(2)D-3 in PBMC of 12 women with p
rimary hyperparathyroidism (PHP), 8 women with hyperparathyroidism sec
ondary to chronic renal failure (SH), 9 women with renal transplant (R
T), and 23 healthy women. The median dissociation constant (K-d) was s
imilar in all three groups of patients and in healthy women (mean +/-
S.D. (range): PHP, 1.2 st 1.0 (0.2-4) x 10(-10) M; SH, 0.6 +/- 0.4 (0.
2-1.2) x 10(-10) M; RT, 1.1 +/- 0.5 (0.4-1.9) x 10(-10) M; controls, 1
.0 st 0.6 (0.3-2.6) x 10(-10) M). However, the maximal binding capacit
y (N-max) was significantly enhanced in PHP (3.9 +/- 1.9 (1.3-7.6) fmo
l/10(7) cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls;
P = 0.0006) and decreased in SH (0.8 +/- 0.5 (0.2-1.6) fmol/10(7) cell
s vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls; P = 0.0001),
whereas no changes were seen in RT (2.3 +/- 0.7 (1.2-3.3) fmol/10(7)
cells vs. 2.3 +/- 0.9 (1.1-4.4) fmol/10(7) cells in controls). In thre
e patients with PHP who were subjected to parathyroidectomy, the calci
triol number came down to normal. Changes of calcitriol receptors in p
rimary and secondary hyperparathyroidism could magnify the consequence
s of disturbances in serum concentration of calcitriol itself and migh
t play an important role in the development of secondary hyperparathyr
oidism in uremia.