25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells
Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Recently, human parathyroid glands have been shown to express 25-hyd...
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| Veröffentlicht in: | Kidney international 2006-08, Vol.70 (4), p.654-659 |
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| description | Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Recently, human parathyroid glands have been shown to express 25-hydroxyvitamin D 1α-hydroxylase (1αOHase), but documentation of the 1αOHase activity in parathyroid cells and its potential role in activating 25-hydroxyvitamin D3 (25(OH)D3) to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have not been reported. The relative potencies of 25(OH)D3 and 1,25(OH)2D3 in reducing PTH secretion and mRNA were determined in primary cultures of bovine parathyroid cells (bPTC). The effects of blocking 1αOHase activity on suppression of PTH mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR) affinities were estimated by intact cell competitive binding assay. Metabolism of 25(OH)D3 by bPTC was assessed using a radioimmunoassay that measures all 1-hydroxylated metabolites of vitamin D. 25(OH)D3 suppressed PTH secretion and mRNA (ED50=2nM), but was several hundred times less potent than 1,25(OH)2D3. The lower potency of 25(OH)D3 correlated with its lower VDR affinity. bPTCs converted 25(OH)D3 to 1-hydroxylated metabolites, but the rate of conversion was low. Inhibition of 1αOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D3-mediated suppression of PTH. Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting catabolism of 25(OH)D3. In conclusion, 25(OH)D3 suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR. |
| doi_str_mv | 10.1038/sj.ki.5000394 |
| format | Article |
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Recently, human parathyroid glands have been shown to express 25-hydroxyvitamin D 1α-hydroxylase (1αOHase), but documentation of the 1αOHase activity in parathyroid cells and its potential role in activating 25-hydroxyvitamin D3 (25(OH)D3) to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have not been reported. The relative potencies of 25(OH)D3 and 1,25(OH)2D3 in reducing PTH secretion and mRNA were determined in primary cultures of bovine parathyroid cells (bPTC). The effects of blocking 1αOHase activity on suppression of PTH mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR) affinities were estimated by intact cell competitive binding assay. Metabolism of 25(OH)D3 by bPTC was assessed using a radioimmunoassay that measures all 1-hydroxylated metabolites of vitamin D. 25(OH)D3 suppressed PTH secretion and mRNA (ED50=2nM), but was several hundred times less potent than 1,25(OH)2D3. The lower potency of 25(OH)D3 correlated with its lower VDR affinity. bPTCs converted 25(OH)D3 to 1-hydroxylated metabolites, but the rate of conversion was low. Inhibition of 1αOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D3-mediated suppression of PTH. Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting catabolism of 25(OH)D3. In conclusion, 25(OH)D3 suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/sj.ki.5000394</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Biological and medical sciences ; calcium ; CYP27B1 ; Medical sciences ; Nephrology. Urinary tract diseases ; parathyroid cells ; PTH ; vitamin D</subject><ispartof>Kidney international, 2006-08, Vol.70 (4), p.654-659</ispartof><rights>2006 International Society of Nephrology</rights><rights>2006 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Aug 2006</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c2964-5623404087ca8cbf74c926a43d44b16e8fe29854aee3a3a311c8f22d253cdbd73</citedby><cites>FETCH-LOGICAL-c2964-5623404087ca8cbf74c926a43d44b16e8fe29854aee3a3a311c8f22d253cdbd73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210124762?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,64385,64389,72469</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18051678$$DView record in Pascal Francis$$Hfree_for_read</backlink></links><search><creatorcontrib>Ritter, C.S.</creatorcontrib><creatorcontrib>Armbrecht, H.J.</creatorcontrib><creatorcontrib>Slatopolsky, E.</creatorcontrib><creatorcontrib>Brown, A.J.</creatorcontrib><title>25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells</title><title>Kidney international</title><description>Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Recently, human parathyroid glands have been shown to express 25-hydroxyvitamin D 1α-hydroxylase (1αOHase), but documentation of the 1αOHase activity in parathyroid cells and its potential role in activating 25-hydroxyvitamin D3 (25(OH)D3) to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have not been reported. The relative potencies of 25(OH)D3 and 1,25(OH)2D3 in reducing PTH secretion and mRNA were determined in primary cultures of bovine parathyroid cells (bPTC). The effects of blocking 1αOHase activity on suppression of PTH mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR) affinities were estimated by intact cell competitive binding assay. Metabolism of 25(OH)D3 by bPTC was assessed using a radioimmunoassay that measures all 1-hydroxylated metabolites of vitamin D. 25(OH)D3 suppressed PTH secretion and mRNA (ED50=2nM), but was several hundred times less potent than 1,25(OH)2D3. The lower potency of 25(OH)D3 correlated with its lower VDR affinity. bPTCs converted 25(OH)D3 to 1-hydroxylated metabolites, but the rate of conversion was low. Inhibition of 1αOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D3-mediated suppression of PTH. Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting catabolism of 25(OH)D3. In conclusion, 25(OH)D3 suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR.</description><subject>Biological and medical sciences</subject><subject>calcium</subject><subject>CYP27B1</subject><subject>Medical sciences</subject><subject>Nephrology. Urinary tract diseases</subject><subject>parathyroid cells</subject><subject>PTH</subject><subject>vitamin D</subject><issn>0085-2538</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNp1kM1Lw0AUxBdRsFaP3hfBY-p-Jpuj-FVB0EPF47LZfaHb1iTuS4v574204Ene4V1-M8MMIZeczTiT5gZXs3WcacaYLNURmXAtZMYLrY_JhDGjM6GlOSVniKuRMaVkE_IhdDYfQmq_h13s3Wds6L2kuO26BIiA9G0xpzg0_RIwInVNoAg-QR_bhlYDrdpdbIB2Lrl-OaQ2Buphs8FzclK7DcLF4U_J--PD4m6evbw-Pd_dvmRelLnKdC6kYoqZwjvjq7pQvhS5UzIoVfEcTA2iNFo5AOnG49ybWogwNvGhCoWckqu9b5fary1gb1ftNjVjpBWccaGKMWFKsj3kU4uYoLZdip8uDZYz-zudxZVdR3uYbuSvD6YOvdvUyTU-4p_IMM3zwoxcsedgbLiLkCz6CI2HEBP43oY2_pPwA4gIgcI</recordid><startdate>20060801</startdate><enddate>20060801</enddate><creator>Ritter, C.S.</creator><creator>Armbrecht, H.J.</creator><creator>Slatopolsky, E.</creator><creator>Brown, A.J.</creator><general>Elsevier Inc</general><general>Nature Publishing</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20060801</creationdate><title>25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells</title><author>Ritter, C.S. ; Armbrecht, H.J. ; Slatopolsky, E. ; Brown, A.J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c2964-5623404087ca8cbf74c926a43d44b16e8fe29854aee3a3a311c8f22d253cdbd73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2006</creationdate><topic>Biological and medical sciences</topic><topic>calcium</topic><topic>CYP27B1</topic><topic>Medical sciences</topic><topic>Nephrology. Urinary tract diseases</topic><topic>parathyroid cells</topic><topic>PTH</topic><topic>vitamin D</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ritter, C.S.</creatorcontrib><creatorcontrib>Armbrecht, H.J.</creatorcontrib><creatorcontrib>Slatopolsky, E.</creatorcontrib><creatorcontrib>Brown, A.J.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Kidney international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ritter, C.S.</au><au>Armbrecht, H.J.</au><au>Slatopolsky, E.</au><au>Brown, A.J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells</atitle><jtitle>Kidney international</jtitle><date>2006-08-01</date><risdate>2006</risdate><volume>70</volume><issue>4</issue><spage>654</spage><epage>659</epage><pages>654-659</pages><issn>0085-2538</issn><eissn>1523-1755</eissn><coden>KDYIA5</coden><abstract>Active vitamin D compounds repress parathyroid hormone (PTH) gene transcription and block chief cell hyperplasia, making them integral tools in the treatment of secondary hyperparathyroidism in patients with chronic kidney disease. Recently, human parathyroid glands have been shown to express 25-hydroxyvitamin D 1α-hydroxylase (1αOHase), but documentation of the 1αOHase activity in parathyroid cells and its potential role in activating 25-hydroxyvitamin D3 (25(OH)D3) to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have not been reported. The relative potencies of 25(OH)D3 and 1,25(OH)2D3 in reducing PTH secretion and mRNA were determined in primary cultures of bovine parathyroid cells (bPTC). The effects of blocking 1αOHase activity on suppression of PTH mRNA and induction of 24-hydroxylase mRNA were examined. Vitamin D receptor (VDR) affinities were estimated by intact cell competitive binding assay. Metabolism of 25(OH)D3 by bPTC was assessed using a radioimmunoassay that measures all 1-hydroxylated metabolites of vitamin D. 25(OH)D3 suppressed PTH secretion and mRNA (ED50=2nM), but was several hundred times less potent than 1,25(OH)2D3. The lower potency of 25(OH)D3 correlated with its lower VDR affinity. bPTCs converted 25(OH)D3 to 1-hydroxylated metabolites, but the rate of conversion was low. Inhibition of 1αOHase with the cytochrome P450 inhibitor clotrimazole did not block 25(OH)D3-mediated suppression of PTH. Clotrimazole enhanced 24-hydroxylase mRNA induction, presumably by inhibiting catabolism of 25(OH)D3. In conclusion, 25(OH)D3 suppresses PTH synthesis by parathyroid cells, possibly by direct activation of the VDR.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><doi>10.1038/sj.ki.5000394</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Biological and medical sciences calcium CYP27B1 Medical sciences Nephrology. Urinary tract diseases parathyroid cells PTH vitamin D |
| title | 25-Hydroxyvitamin D3 suppresses PTH synthesis and secretion by bovine parathyroid cells |
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