Endocrinology, Vol 118, 1808-1813, Copyright © 1986 by Endocrine Society
Impaired parathyroid hormone-stimulated adenosine 3',5'-monophosphate release by isolated perfused bones obtained from vitamin D-deficient rats
T Sugimoto, M Fukase, M Tsutsumi, M Nakada, R Hishikawa, T Tsunenari, Y Yoshimoto and T Fujita
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.
