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 D-replete (+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, indicating partial restoration of the impaired response to PTH in -D rats. These data indicate that skeletal refractoriness to PTH in vitamin D-deficient animals might, in part, be due to the impaired activation of adenylate cyclase, which cannot be explained entirely by hypocalcemia or associated secondary hyperparathyroidism. Vitamin D deficiency per se, therefore, may play a key role in the impaired cAMP response to PTH.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism* / Q000652:urine; D005269:Femur / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014807:Vitamin D / Q000502:physiology; D014808:Vitamin D Deficiency / Q000378:metabolism*
D010281:Parathyroid Hormone; D014807:Vitamin D; D000242:Cyclic AMP