Regulation of ornithine decarboxylase by parathyroid hormone in osteoblastic cell systems.
Parathyroid hormone (PTH) has been shown to induce osteoblastic activity via a complex signal transduction process which is mediated either by cAMP or cytosolic calcium ([Ca2+]i), or a combination thereof. One of the PTH functions in osteoblasts is the induction of ornithine decarboxylase (ODC) activity. We have analyzed the second messengers involved in this process. 8-Bromo cAMP, a cAMP derivative, enhanced ODC activity in UMR106-01 osteoblastic cell system. The calcium ionophore A23187 and the protein kinase stimulator phorbol-12-myristate 13-acetate did not alter ODC activity. ODC activity was increased by bPTH-(1-34), PGE1, and PGE2 which stimulated both cAMP and [Ca2+]i. In contrast, PTH-(2-34), propionyl bPTH-(2-34), bPTH-(3-34), bPTH-(7-34), and PGF2 alpha, which only enhanced [Ca2+]i but not cAMP, had no effect on ODC activity. Thus, the stimulation of ODC in UMR106 cells by PTH appeared to be mediated primarily via the cAMP signal transduction pathway, and the mere increase in intracellular calcium could not account for the stimulation of ODC activity. ODC mRNA level was found to be increased by PTH treatment. Therefore, translation of ODC may be stimulated by PTH. Moreover, PTH also stimulated ODC antizyme activity, suggesting that the ODC degradation rate was increased.
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Division of Bone and Mineral Metabolism and Endocrinology, Jewish Hospital, Washington University Medical Center, St. Louis, Missouri 63110.
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D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D004790:Enzyme Induction; D006728:Hormones / Q000494:pharmacology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D010006:Osteoblasts / Q000187:drug effects* / Q000201:enzymology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011458:Prostaglandins E / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D006728:Hormones; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011458:Prostaglandins E; D012333:RNA, Messenger; C025076:parathyroid hormone (1-34), bovine; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000001:Calcimycin; D015237:Dinoprost; D000242:Cyclic AMP; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium