Impaired Parathyroid Hormone-Stimulated Adenosine 3′,5′-Monophosphate Release by Isolated Perfused Bones Obtained from Vitamin D-Deficient Rats*

The present studies were designed to explore the mechanism underlying skeletal refractoriness to PTH in a vitamin D-deficient animal by assessment of PTH-stimulated cAMP release from isolated perfused bone. In vitamin D-deficient (−D) rats both basal and PTH-stimulated cAMP release were markedly diminished, compared with that in vitamin Dreplete (+D) rats. Isolated perfused bones from −D rats that had undergone parathyroidectomy 2 days before death still showed reduced cAMP release in response to PTH, compared with +D bones. To investigate which factors in terms of Ca, endogenous PTH, or vitamin D might primarily be responsible for the impaired PTH-stimulated cAMP release from −D bones, some −D rats were switched to a diet identical to the vitamin D-deficient diet but with high Ca content (4%) for 2 or 5 weeks before death. This schedule maintained normocalcemia despite vitamin D deficiency. PTH-stimulated cAMP release in these rats was increased to a level intermediate between that in −D rats and +D rats...