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Parathyroid hormone (PTH) stimulates bone formation when injected daily but causes severe bone loss with continuous infusion. The mechanism of its paradoxical effects is still elusive. In this study, we compared changes in the gene expression profile in bone induced by intermittent or continuous treatment with three different PTH peptides, PTH-(1-34), -(1-31), and -(3-34), in Sprague-Dawley female rats. PTH-(1-34) regulated numerous genes (∼1,000), but differentially, in both regimes. PTH-(1-31) regulated a similar number of genes in the intermittent regimen but fewer in the continuous regimen, consistent with its less potent catabolic effect. PTH-(3-34) regulated very few genes in both regimes, which suggests the protein kinase C pathway plays a limited role in mediating the dual effects of PTH, whereas the cAMP-dependent protein kinase A pathway appears to predominate. In the intermittent treatment, many …