Clinical Trial: Regulation of Vitamin D Receptor (VDR),Calcium Sensing Receptor (CaSR), Cyclin D1,Ki67 and Proliferating Cell Nuclear Antigen (PCNA) in Primary Hyperparathyroidism
Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational
Official Title: Transcriptional and Translational Regulation of Vitamin D Receptor (VDR) and Calcium Sensing Receptor (CaSR) in Patients With Sporadic Primary Hyperparathyroidism
Brief Summary: The present study is designed to examine the expression of VDR, CaSR, PTH, Cyclin D1, Ki67 and PCNA and to find out its relationship with clinical parameters in parathyroid adenomas. Examination of the contribution of genes expression can elucidate the critical link between proliferation and functional abnormalities in parathyroid adenomas. Alternative to DNA and RNA, protein expression can provide a better understanding of this disease.
Detailed Summary:
Introduction:
Primary hyperparathyroidism (PHPT) is the third most frequent endocrine disorder, after diabetes mellitus and thyroid disorders, that predominantly affects postmenopausal women, with an incidence of 1 -5 in 1000 people. It can occur at any age though young people are rarely affected. PHPT is characterized by hypersecretion of parathyroid hormone (PTH) and resultant hypercalcemia. Most cases of PHPT (>85%) result from a solitary adenoma in one of the parathyroid glands. Multi-gland hyperplasia is found in about 10-15% of the patients while carcinoma occurs rarely (1-2%).
The parathyroid glands regulate calcium homeostasis. The major target organs for parathyroid hormone (PTH) are bone and the kidneys. PTH increases bone resorption to mobilize calcium into the circulation. In the kidney, PTH enhances calcium reabsorption and increases phosphate excretion. PTH also stimulates renal production of 1α,25-dihydroxyvitamin D [1,25(OH)2D], which in turn enhances intestinal absorption of calcium. Thus, the physiological effects of PTH are to increase the concentration of calcium in the circulation. Negative feedback from calcium and 1,25(OH)2D modulate parathyroid function. These effects are mediated via the calcium-sensing receptor (CaSR) expressed on the parathyroid cell surface. Similarly, 1,25(OH)2D, acts through vitamin D receptor (VDR) and suppresses PTH synthesis and secretion . Thus, PTH secretion is tightly coupled to the parathyroid cell's ambient calcium level.
Increased parathyroid cell proliferation and decreased calcium-mediated control of the PTH secretion are characteristic findings in all types of hyperparathyroidism (1-4). Calcium via its receptor, the CaSR and the 1,25(OH)2D-VDR complex are the most important regulators, in this respect. Decre
Sponsor: Postgraduate Institute of Medical Education and Research
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Information By: Postgraduate Institute of Medical Education and Research
Dates:
Date Received: October 26, 2010
Date Started: October 2007
Date Completion: June 2013
Last Updated: July 19, 2012
Last Verified: July 2012
