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-o(2+)) 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-o(2+) 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 Ca-o(2+) of PTHrP could still be detected. These results elevated cytosolic free calcium, the stimulation by Ca, indicate that increasing Ca-o(2+) 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.