Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Binding of highly concentrated maxacalcitol to the nuclear vitamin D receptors of parathyroid cells.

Shiizaki K, Hayakawa N, Imazeki I, Hatamura I, Okada T, Negi S, Sakaguchi T, Shigematsu T, Akizawa T

Division of Nephrology and Blood Purification Medicine, Wakayama Medical University, Wakayama 641-0012, Japan. shiizaki@wakayama-med.ac.jp

BACKGROUND: Injection of maxacalcitol (OCT) directly into the parathyroid gland (PTG) is a clinically safe and effective treatment for advanced secondary hyperparathyroidism (A-SHPT) resistant to conventional medical treatment. In the present study, the degree of nuclear localization of directly injected OCT in parathyroid cells (PTC) was investigated by microautoradiography (mARG) in a model of A-SHPT. METHODS: The 5/6 nephrectomized Sprague-Dawley rats were fed a high-phosphate and low-calcium diet for 8 weeks and consequently the level of vitamin D receptor (VDR) in their PTC severely decreased. The bilateral PTG were surgically exposed and only the left gland were directly injected with 3H-OCT (DI-3H-OCT). The time course of the changes in both radioactivity and localization of 3H-OCT in the bilateral glands was analysed using a bioimaging analyser system and mARG, respectively. A very high dose of unlabelled calcitriol was administered intravenously (IV-1,25D3) prior to DI-3H-OCT, as a competitive study. RESULTS: Peak radioactivity levels in the directly injected and intact PTG occured immediately and 1 h, respectively, after DI-3H-OCT, and the difference was about 50-fold higher in the treated gland. The of mARG showed a marked concentration of silver grains in the nuclei of PTC in the gland treated with DI-3H-OCT and that concentration was significantly suppressed by IV-1,25D3. CONCLUSIONS: Direct injection of OCT into the PTG enables the administration of the highly concentrated drug for specific binding to nuclear vitamin D binding sites, including VDR of PTC, which markedly suppresses the parathyroid hormone, improves the response to calcium and vitamin D and induces apoptosis in PTC.

Published 26 March 2007 in Nephrol Dial Transplant, 22(4): 1078-86.
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