Effects of parathyroid hormone on the accumulation of cyclic AMP in bone of vitamin D-deficient rats.

The mechanism of skeletal refractoriness to parathyroid hormone (PTH) in vitamine D-deficient animals was studied in terms of the adenylate cyclase-cyclic AMP system in rat calvaria. In vitamin D-deficient, thyroparathyroidectomized rats, plasma calcium concentration was not elevated by iv administration of PTH, while responsiveness to the hormone was recovered within 24 h after a single dose (2.5 mug) of vitamin D3. In spite of the remarkable dependency of PTH on vitamin D for mobilization of calcium from bone, PTH stimulated adenylate cyclase activity in particulate bone cell fractions in vitro. PTH also enhanced the levels of cyclic AMP in the skeletal tissues of vitamin D-deficient rats in vivo and in vitro to an extent similar to those found in rats given 2.5 mug of D3. Administration of theophylline or dibutyryl cyclic AMP to the vitamin D-deficient rats did not cause any significant hypercalcemic effects, while these drugs enhanced plasma calcium concentration significantly in the rats given vitamin D3. These data strongly indicate that the cause of the skeletal refractoriness to PTH in vitamin D-deficient animals is not a defective activation of adenylate cyclase, but must be related to a later step or steps in the biochemical events leading to bone cell activation.