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The DNA flanking the 5[prime] sequence of the mouse l[Alpha]-hydroxylase gene has been cloned and sequenced. A TATA box has been located at -30 bp and aCCAAT box has been located at -79 bp. The gene's promoter activity has been demonstrated by using a luciferase reporter gene construct transfected into a modified pig kidney cell line, AOK-B50. Parathyroid hormone stimulates this promoter-directed synthesis of luciferase by 17-fold, whereas forskolin stimulates it by 3-fold. The action of parathyroid hormone is concentration-dependent. 1,25-Dihydroxyvitamin D3 does not suppress basal promoter activity and marginally suppresses parathyroid hormone-driven luciferase reporter activity. The promoter has three potential cAMP-responsive element sites, and two perfect and one imperfect AP-1 sites, while no DR-3 was detected. These results indicate that parathyroid hormone stimulates 25-hydroxyvitamin D3-1a[Alpha]-hydroxylase by acting on the promoter of the 1[Alpha]-hydroxylase gene.

The article discusses research which determined whether genetic profiles of the vitamin D receptor (VDR) promoter influence the effect of milk/dairy products consumption on bone accrual. It references a study by Laure Esterle and colleagues, published on the March 16, 2009 online issue of the "Journal of Bone and Mineral Research." The lumbar spine bone marrow cells (BMC) and bone mineral density (BMD), milk/dairy products and calcium intakes of 117 healthy European peri- and postmenarcheal girls were evaluated.

Analysis the activation of parathyroid hormone of the 25-hydroxyvitamin D-3-1...-hydroxylase gene promoter. Information on the deoxyribonucleic acid (DNA) flanking the 5' sequence of the muse 1...-hydroxylase gene; Demonstration of the gene's promoter activity; Indication that parathyroid hormone simulates 25-hydroxyvitamin.

If both rapid and genomic pathways may co-exist in the same cell, the involvement of the nuclear vitamin D receptor (VDR) in the rapid effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) remains unclear. We therefore studied rapid and long term effects of 1,25-(OH)2D3 in cultured skin fibroblasts from three patients with severe vitamin D-resistant rickets and one age-matched control. Patients bear homozygous missense VDR mutations that abolished either VDR binding to DNA (patient 1, mutation K45E) or its stable ligand binding (patients 2 and 3, mutation W286R). In patient I cells, 1,25-(OH)2D3 (1 pM-10 nM) had no effect on either intracellular calcium or 24-hydroxylase (enzyme activity and mRNA expression). In contrast, cells bearing the W286R mutation had calcium responses to 1,25-(OH)2D3 (profile and magnitude) and 24-hydroxylase responses to low (1 pM-100 pM) 1,25-(OH)2D3 concentrations (activity, CYP24, and ferredoxin mRNAs) similar to those of controls. The blocker of Ca2+ channels, verapamil, impeded both rapid (calcium) and long term (24-hydroxylase activity, CYP24, and ferredoxin mRNAs) responses in patient and control fibroblasts. The MEK ½ kinase inhibitor PD98059 also blocked the CYP24 mRNA response. Taken together, these results suggest that 1,25-(OH)2D3 rapid effects require the presence of VDR and control, in part, the first step of 1,25-(OH)2D3 catabolism via increased mRNA expression of the CYP24 and ferredoxin genes in the 24-hydroxylase complex. [ABSTRACT FROM AUTHOR]