Localization of 1,25-dihydroxyvitamin D3 receptor (VDR) expression in human prostate.
1,25-dihydroxyvitamin D3 (1,25(OH)2D3) has been found to have a variety of physiological functions, including effects on growth and differentiation in normal and malignant cells. The antiproliferative effects of 1,25(OH)2D3 are reported to be mediated through the genomic signaling pathway by binding to a specific high affinity receptor protein, the 1,25-dihydroxyvitamin D3 receptor (VDR). VDR has been localized in a variety of tissues, but little is known about VDR distribution in human prostate. In this study, we raised an antibody against a synthetic peptide corresponding to amino acids 10-24 of human vitamin D receptor. The sequence selected for immunization is identical in human, rat and mouse VDR. Based on this antibody, we developed an immunohistochemical method suitable for studying VDR expression in paraffin-embedded tissue. The immunohistochemical staining was verified using classical target organs for vitamin D (kidney, intestine, skin). With this method, we studied VDR localization on paraffin-embedded human prostatic tissue obtained from 8 patients undergoing radical prostatectomy for urinary bladder cancer and demonstrate VDR expression in the secretory epithelial and few stromal cells of human prostate. The nuclear staining in the secretory epithelial cells was concentrated near the nuclear membrane and in discrete foci in the nucleoplasm. This suggests that effects of 1,25-dihydroxyvitamin D3 are mediated through VDR in these cells. Moreover our result indicates that there are strong variations in VDR expression between prostatic samples.
Graduate School of Steroid Research, Department of Anatomy, University of Tampere, Finland. lomeki@uta.fi
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Kivineva
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Bläuer
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Syvälä
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Tammela
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Tuohimaa
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D002467:Cell Nucleus / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012516:Osteosarcoma; D010446:Peptide Fragments / Q000276:immunology; D011467:Prostate / Q000737:chemistry* / Q000648:ultrastructure; D051381:Rats; D018167:Receptors, Calcitriol / Q000032:analysis* / Q000737:chemistry / Q000276:immunology; D017154:Stromal Cells / Q000737:chemistry; D014018:Tissue Distribution; D016610:Tissue Embedding; D014407:Tumor Cells, Cultured
D000906:Antibodies; D010446:Peptide Fragments; D018167:Receptors, Calcitriol