Calcium stimulates parathyroid hormone-related protein production in Leydig tumor cells through a putative cation-sensing mechanism.
The production of parathyroid hormone-related protein (PTHrP) is regulated by a variety of hormones and growth factors. Previous research has shown that several PTHrP-producing cells are influenced by extracellular calcium (Ca(2+)(o)) concentration, with elevated levels increasing PTH-like activity released by cultured H500 rat Leydig tumor cells through a post-transcriptional mechanism. We have investigated the hypothesis that calcium stimulates PTHrP production in H500 cells by interacting with a cell membrane-associated cation-sensing receptor. Besides increased Ca(2+)(o) concentration, magnesium and the polycationic antibiotic neomycin also increased PTHrP production in a concentration-dependent manner. In the presence of the calcium ionophore, ionomycin, which markedly elevated cytosolic free calcium, the stimulation by Ca(2+)(o) of PTHrP could still be detected. These results indicate that increasing Ca(2+)(o) stimulates PTHrP production, possibly through a putative cell membrane-associated calcium-sensing mechanism. RT-PCR revealed the presence of a very small amount of calcium-sensing receptor coding mRNA.
Buchs
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N
Division of Bone Diseases, WHO Collaborating Center for Osteoporosis and Bone Diseases, Department of Internal Medicine, University Hospital of Geneva, 1211 Geneva 14, Switzerland.
Manen
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D
Bonjour
J P
JP
Rizzoli
R
R
D000818:Animals; D015152:Blotting, Northern; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D007984:Leydig Cell Tumor / Q000201:enzymology / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008297:Male; D051379:Mice; D009355:Neomycin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010281:Parathyroid Hormone / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011500:Protein Synthesis Inhibitors; D012334:RNA, Neoplasm; D011493:Protein Kinase C; D009355:Neomycin; D008274:Magnesium; D002118:Calcium