Retinoic acid receptors are expressed in human primary astrocytes and their agonists inhibit parathyroid hormone-related peptide expression and secretion.
We isolated, by RT-PCR, partial cDNAs encoding retinoic acid receptor (RAR) isoforms, alpha, beta and gamma, in human primary astrocytes and confirmed their expression by western analysis. A naturally occurring RAR agonist, all-trans retinoic acid and a synthetic RAR agonist, [(E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthylenyl)-1-propenyl]benzoic acid], each inhibited PTHrP secretion with EC(50) values of approximately 25 and 250 nM, respectively. The two may act at a transcriptional level as assessed by Northern analysis. Thus retinoids, most likely acting via RARs, inhibit parathyroid hormone-related protein expression and secretion in human primary astrocytes, with a synthetic RAR-specific agonist being more potent than a naturally occurring RAR agonist.
Chattopadhyay
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Endocrine-Hypertension Division and Membrane Biology Program, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. nchattopadhyay@rics.bwh.harvard.edu
Brown
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EM
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology*; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D012176:Retinoids / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*
D001565:Benzoates; D009419:Nerve Tissue Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D014212:Tretinoin; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid