Effects of parathyroid hormone on ornithine decarboxylase activity in human osteosarcoma cells

Ornithine decarboxylase (ODC) is a rate-limiting enzyme of the biosynthesis of polyamines, which are important in cell growth and differentiation. Here, we studied whether parathyroid hormone (PTH) affects the induction of ODC and the proliferation of the human osteoblast-like cell line SaOS2, which is sensitive to PTH. In confluent cells, ODC activity was not detected, but activity was significantly induced by fresh medium, with maximum activity 6 h after the change. PTH potentiated this enzyme induction in a dose-dependent manner at 10(-9) and 10(-8) M at which range the intracellular cAMP level also rose. Dibutyryl cAMP, cholera toxin, and 3-isobutyl-1-methylxanthine each caused an increase in ODC activity similar to that with PTH. The half-life of enzyme activity was about 30 min and was not changed by the addition of PTH. mRNA coding for ODC was detected in the confluent cells and its concentration was increased two- to threefold by the fresh medium. No further increase in mRNA occurred when PTH was added. At 48 h after the change of medium, PTH inhibited the DNA synthesis induced by fresh medium. These results suggest that the increase in ODC activity caused by PTH was caused by enhancement of cAMP synthesis, and that this augmentation involves post-transcriptional regulation.