ACTIVATION OF PHOSPHOINOSITIDE METABOLISM BY PARATHYROID-HORMONE IN GROWTH-PLATE CHONDROCYTES

Parathyroid hormone (PTH) is one of the most potent stimulators of gro wth plate chondrocyte mitogenesis that has been reported. However, stu dy of the second messenger signaling mechanisms involved in the transd uction of the hormone's effects on these cells is incomplete. Our data indicate that in addition to stimulating cyclic adenosine-3'5'-monoph osphate metabolism, PTH also activates the phosphoinositide cascade, t he pathway responsible for the generation of inositol-1,4,5-trisphosph ate dependent Ca2+ signals. Our conclusion that PTH activates the phos phoinositide cascade is based on data that demonstrate: (1) the Ca2+ t ransients evoked by the hormone are dependent on intracellular Ca2+ st ores; (2) the hormone stimulates the release of radiolabeled inositol phosphates from GPC plasma membranes; and (3) the hormone stimulates a greater than 8-fold increase in cytosolic inositol-1,4,5-trisphosphat e pool size.