vitamin-d-2 and seocalcitol

Vitamin D3 is modified by vitamin D3-25-hydroxylase in the liver and 25-hydroxyvitamin D3-1 alpha-hydroxylase in the kidney to form the active metabolite 1 alpha,25-dihydroxyvitamin D3. The binding of 1 alpha,25-dihydroxyvitamin D3 to the vitamin D receptor (VDR), a nuclear receptor, activates VDR to interact with retinoid X receptor (RXR) and form the VDR/RXR/co-factor complex, which binds to vitamin D response elements in the promoter region of target genes to regulate gene transcription. 1 alpha,25-dihydroxyvitamin D3 regulates the homeostasis of calcium and phosphorus, and also controls the expression of parathyroid hormone. Chronic renal disease is characterized by reduced synthesis of 1 alpha,25-dihydroxyvitamin D3, inadequate renal phosphate clearance and calcium imbalance, over-stimulation of the parathyroid gland, and increased parathyroid hormone synthesis. This secondary hyperparathyroidism (HPT) can cause renal osteodystrophy unless treated. Several vitamin D analogs are currently available or under investigation for the treatment of secondary HPT, psoriasis and osteoporosis. Additional clinical studies are being conducted for a variety of indications, including bone diseases, cell proliferation disorders and autoimmune diseases. Different vitamin D analogs seem to exhibit differential effects as exemplified by the survival benefit provided by paricalcitol over 1 alpha,25-dihydroxyvitamin D3 for end-stage renal disease patients on hemodialysis. Elucidation of the mechanism of action for the different vitamin D analogs will enhance our understanding of the vitamin D pathway and improve therapeutic uses of these analogs. This review discusses recent progress on the use of vitamin D and its analogs in the management of HPT secondary to chronic renal disease.

Topics: Calcitriol; Clinical Trials as Topic; Ergocalciferols; Humans; Hyperparathyroidism, Secondary; Immunosuppressive Agents; Kidney Failure, Chronic; Vitamin D

Atherosclerosis is the principal cause of myocardial infarction, stroke, and peripheral vascular disease, accounting for nearly half of all mortality in developed countries. The excessive growth of vascular smooth muscle cells is an important component in the development of atherosclerotic lesion. The direct effect of calcitriol and vitamin D analogs on the VSMCs proliferation is not clear. In this study we have analysed if calcitriol, Paricalcitol (19-nor-1,25-dihydroxy-vitamin D2) and EB1089 (experimental analog used as anticancerous) modify proliferation and the expression of vitamin D receptor (VDR) gene that is regulated at the transcriptional level by itself in the VSMCs. VSMCs proliferation was analysed by BrdU incorporation and VDR gene expression using RT-PCR. VSMCs proliferation was stimulated when calcitriol was added to the culture. VSMCs proliferation was significantly lower with analogs at the same dose. With regard to the functional study, the expression of VDR gene was upregulated by calcitriol at a concentration of 100 nM. There were no changes in this expression with the analogs. In conclusion, calcitriol, do not modify VSMCs proliferation. Therefore, Paricalcitol could have a minor proliferating effect on the wall of vessels that vitamin D.

Topics: Animals; Aorta; Calcitriol; Cell Division; Cells, Cultured; DNA Replication; Ergocalciferols; Feedback, Physiological; Gene Expression Regulation; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; Receptors, Calcitriol; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stimulation, Chemical; Transcription, Genetic