| A non-calcemic analog of 1 alpha,25 dihydroxy vitamin D(3) (JKF) upregulates the induction of creatine kinase B by 17 beta estradiol in osteoblast-like ROS 17/2.8 cells and in rat diaphysis. | |
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MedLine Citation:
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PMID: 11457658 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have reported that multiple treatments with so-called 'non-hypercalcemic' analogs of 1 alpha,25(OH)(2) vitamin D(3) (1,25(OH)(2)D(3)) stimulate the specific activity of creatine kinase BB (CK) in ROS 17/2.8 osteoblast-like cells, and that pretreatment with these analogs upregulates responsiveness and sensitivity to 17 beta estradiol (E(2)) for the induction of CK. However, since the analogs showed toxicity in vivo, we have now studied the action of a demonstrably non-calcemic hybrid analog of vitamin D in ROS 17/2.8 cells, and prepubertal rats. The analog JKF was designed to separate its calcemic activity from other biological activities by combining a calcemic-lowering 1-hydroxymethyl group with a potentiating C, D-ring side chain modification including 24 difluoronation. Treatment with 1 pM JKF alone significantly stimulated CK specific activity at 4 h by 30+/-10%. However after three daily pretreatments, JKF upregulated the extent of induction by 30 nM E(2) by 33% at 1 pM and by 97% at 1 nM; the E(2) dose needed for a significant stimulation of CK activity was lowered to 30 pM. The action of the SERMS tamoxifen, tamoxifen methiodide and raloxifene, at 3 microM, was also upregulated by three daily pretreatments with 1 nM JKF; unexpectedly, this pretreatment prevented the inhibition of E(2) stimulation by the SERMS. Upregulation of E(2) action by 1 nM JKF was inhibited by 1 nM ZK159222, an inhibitor of the nuclear action of 1,25(OH)(2)D(3). In vivo, three daily injections of 0.05 ng/g body weight of JKF augmented the response of prepubertal female rat diaphysis and epiphysis to E(2). Therefore, demonstrably non-calcemic analogs of 1,25(OH)(2)D(3) may have potential for use in combination with estrogens or SERMS in the prevention and/or treatment of metabolic bone diseases such as postmenopausal osteoporosis. |
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Authors:
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D Somjen; A Waisman; J K Lee; G H Posner; A M Kaye |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of steroid biochemistry and molecular biology Volume: 77 ISSN: 0960-0760 ISO Abbreviation: J. Steroid Biochem. Mol. Biol. Publication Date: 2001 Jun |
Date Detail:
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Created Date: 2001-07-17 Completed Date: 2001-08-23 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 9015483 Medline TA: J Steroid Biochem Mol Biol Country: England |
Other Details:
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Languages: eng Pagination: 205-12 Citation Subset: IM |
Affiliation:
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Institute of Endocrinology, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 64239, Israel. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antineoplastic Agents / pharmacology Calcitriol / analogs & derivatives, pharmacology* Creatine Kinase / biosynthesis* Creatine Kinase, BB Form Diaphyses / drug effects*, enzymology Drug Interactions Enzyme Induction / drug effects Estradiol / pharmacology* Growth Plate / drug effects, enzymology Isoenzymes / biosynthesis* Male Osteoblasts / drug effects*, enzymology Rats Rats, Wistar Receptors, Estrogen / metabolism Selective Estrogen Receptor Modulators / metabolism Steroid Hydroxylases / chemistry, pharmacology Tumor Cells, Cultured Up-Regulation Vitamin D / analogs & derivatives |
| Grant Support | |
ID/Acronym/Agency:
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CA-44530/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents; 0/Isoenzymes; 0/JK 1624F2-1; 0/Receptors, Estrogen; 0/Selective Estrogen Receptor Modulators; 1406-16-2/Vitamin D; 32222-06-3/Calcitriol; 50-28-2/Estradiol; EC 1.14.-/Steroid Hydroxylases; EC 1.14.-/vitamin D 1-alpha hydroxylase; EC 2.7.3.2/Creatine Kinase; EC 2.7.3.2/Creatine Kinase, BB Form |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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