Abstract
Vitamin D and parathyroid hormone (PTH) constitute the main regulators of systemic calcium homeostasis. As well as its calcaemic effects, active vitamin D3(1,25(OH)2D3) has a direct regulatory role on parathyroid cells. Active vitamin D3 acts via its receptor (VDR), and binding of the ligand-receptor complex to specific promotor regions of the PTH gene inhibits transcription1. Active vitamin D3 constitutes a principal regulator of parathyroid cell growth2,3, and polymorphism in the VDR gene has recently been related to bone mineral density and suggested as predisposing to osteoporosis4. Impaired effects of active vitamin D3 may contribute to the relatively enhanced secretion and cell proliferation seen in hyperparathyroidism (HPT). Indeed, VDR dysfunction, of essentially unknown character, has been demonstrated in the pathological parathyroid tissue of primary HPT as well as HPT secondary to uraemia5,6. Consistent with the essential role of active vitamin D3 in parathyroid regulation, the VDR gene polymorphism was studied in 90 postmenopausal women with primary hyperparathyroidism. The VDR genotype bb was found in 60.0% of HPT patients and in 33.3% of the postmenopausal female controls (P < 0.001). As the b allele has been linked to decreased transcriptional activity or messenger RNA stability4,7, reduced VDR expression may impede regulatory actions of vitamin D and may contribute to parathyroid tumorigenesis in these patients.
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Demay, M.B., Kiernan, M.S., DeLuca, H.F. & Kronenberg, H.M. Sequences in the human parathyroid hormone gene that bind the 1, 25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1, 25-dihydroxyvitamin D3. Proc. natn. Acad. Sci. U. S. A. 89, 8097–8101 (1992).
Nygren, P. et al. 1, 25(OH)2D3 inhibits hormone secretion and proliferation but not functional dedifferentiation of cultured bovine parathyroid cells. Calcif. Tissue Int. 43, 213–218 (1988).
Kremer, R., Bolivar, I., Goltzman, D. & Hendy, G.N. Influence of calcium and 1, 5-dihydroxycholecalciferol on proliferation and proto-oncogene expression in primary cultures of bovine parathyroid cells. Endocrinology 125, 935–941 (1989).
Morrison, N.A. et al. Prediction of bone density from vitamin D receptor alleles. Nature 367, 284–287 (1994).
Karmali, R., Farrow, S., Hewison, M., Barker, S. & O'Riordan, J.L.H. Effects of 1, 25-dihydroxyvitamin D3 and cortisol on bovine and human parathyroid cells. J. Endocr. 123, 137–142 (1989).
Fukuda, N. et al. Decreased 1, 25-dihydroxyvitamin D3, receptor density is associated with a more severe form of parathyroid hyperplasia in chronic uremic patients. J. din. Invest. 92, 1436–1443 (1993).
Farrow, S. Allelic variations and the vitamin D receptor. Lancet 343, 1242 (1994).
Hustmyer, F., Peacock, M., Hui, S., Johnston, C. & Christian, J. Bone mineral density in relation to polymorphism at the vitamin D receptor locus. J. clin. Invest. 94, 2130–2134 (1994).
Kröger, H. et al. Vitamin D receptor genotypes and bone mineral density. Lancet 345, 1238 (1995).
Riggs, B. et al. The contribution of vitamin D receptor gene alleles to the determination of bone mineral density in normal and osteoporotic women. J. Bone miner. Res. 10, 991–996 (1995).
Melhus, H. et al. Vitamin D receptor genotypes in osteoporosis. Lancet 344, 949–950 (1994).
Arnold, A., Staunton, C.E., Kim, H.G., Gaz, R.D. & Kronenberg, H.M. Monoclonality and abnormal parathyroid hormone genes in parathyroid adenomas. New Engl. J. Med. 318, 658–662 (1988).
Arnold, A. Genetic basis of endocrine disease 5. Molecular genetics of parathyroid gland neoplasia. J. clin. Endocr. Metab. 77, 1108–1112 (1993).
Arnold, A. et al. Molecular cloning and chromosomal mapping of DNA rearranged with the parathyroid hormone gene in parathyroid adenoma. J. clin. Invest. 83, 2034–2040 (1989).
Friedman, E. et al. Allelic loss from chromosome 11 in parathyroid tumors. Cancer Res. 52, 6804–6809 (1992).
Palmér, M., Jakobsson, S., Åkerstrom, G. & Ljunghall, S. Prevalence of hypercal-cemia in a health survey: A fourteen-year follow-up study of serum calcium values. Eur. Clin. Invest. 18, 39–46 (1988).
Åkerstrom, G. et al. Histologic parathyroid abnormalities in an autopsy series. Hum. Path. 17, 520–527 (1986).
Beelman, C.A. & Parker, R. Degradation of mRNA in eukaryotes. Cell 81, 179–183 (1995).
Howard, G. et al. Genetic influences on bone density: Physiological correlates of vitamin D receptor alleles in premenopausal women. J. clin. Endocr. Metab. 80, 2800–2805 (1995).
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Carling, T., Kindmark, A., Hellman, P. et al. Vitamin D receptor genotypes in primary hyperparathyroidism. Nat Med 1, 1309–1311 (1995). https://doi.org/10.1038/nm1295-1309
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DOI: https://doi.org/10.1038/nm1295-1309
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