Effects of Parathyroid Hormone on the Accumulation of Cyclic AMP in Bone of Vitamin D-Deficient Rats

Abstract

The mechanism of skeletal refractorinessto parathyroid hormone (PTH) in vitaminD-deficient animals was studied in terms of theadenylate eyclase-cyclic AMP system in rat calvaria.In vitamin D-deficient, thyroparathyroidectomizedrats, plasma calcium concentration wasnot elevated by iv administration of PTH, whileresponsiveness to the hormone was recoveredwithin 24 h after a single dose (2.5 μg) of vitaminD₃. In spite of the remarkable dependency ofPTH on vitamin D for mobilization of calciumfrom bone, PTH stimulated adenylate cyclase activityin particulate bone cell fractions in vitro.PTH also enhanced the levels of cyclic AMPin the skeletal tissues of vitamin D-deficient ratsin vivo and in vitro to an extent similar to thosefound in rats given 2.5 μg of D₃. Administrationof theophylline or dibutyryl cyclic AMP tothe vitamin D-deficient rats did not cause anysignificant hypercalcemic effects, while these drugsenhanced plasma calcium concentration significantlyin the rats given vitamin D₃. These data stronglyindicate that the cause of the skeletal refractorinessto PTH in vitamin D-deficient animals isnot a defective activation of adenylate cyclase,but must be related to a later step or steps inthe biochemical events leading to bone cell activation. (Endocrinology97: 1288, 1975)