1,25-Dihydroxyvitamin D3 receptors in peripheral blood mononuclear cells from patients with primary and secondary hyperparathyroidism

Abstract

A decreased number of calcitriol (1,25(OH)₂D₃) receptors has been observed in parathyroid glands of uremic animals. In humans, studies carried out in surgically removed parathyroid glands have shown that calcitriol binding is higher in primary than in secondary hyperparathyroidism. Since specific receptors for calcitriol have been described in peripheral blood mononuclear cells (PBMC), we have investigated the specific uptake of ³H-labelled l,25(OH)₂D₃ in PBMC of 12 women with primary hyperparathyroidism (PHP), 8 women with hyperparathyroidism secondary to chronic renal failure (SH), 9 women with renal transplant (RT), and 23 healthy women. The median dissociation constant (K_d) was similar in all three groups of patients and in healthy women (mean ± S.D. (range): PHP, 1.2 ± 1.0 (0.2–4) × 10⁻¹⁰ M; SH, 0.6 ± 0.4 (0.2–1.2) × 10⁻¹⁰ M; RT, 1.1 ± 0.5 (0.4–1.9) × 10⁻¹⁰ M; controls, 1.0 ± 0.6 (0.3–2.6) × 10⁻¹⁰ M). However, the maximal binding capacity (N_max) was significantly enhanced in PHP (3.9 ± 1.9 (1.3–7.6) fmol/10⁷ cells vs. 2.3 ± 0.9 (1.1–4.4) fmol/10⁷ cells in controls; P = 0.0006) and decreased in SH (0.8 ± 0.5 (0.2–1.6) fmol/10⁷ cells vs. 2.3 ± 0.9 (1.1–4.4) fmol/10⁷ cells in controls; P = 0.0001), whereas no changes were seen in RT (2.3 ± 0.7 (1.2–3.3) fmol/10⁷ cells vs. 2.3 ± 0.9 (1.1–4.4) fmol/10⁷ cells in controls). In three patients with PHP who were subjected to parathyroidectomy, the calcitriol number came down to normal. Changes of calcitriol receptors in primary and secondary hyperparathyroidism could magnify the consequences of disturbances in serum concentration of calcitriol itself and might play an important role in the development of secondary hyperparathyroidism in uremia.