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

Third Division, Department of Medicine, Kobe University School of Medicine Kobe 650, Japan

Address all correspondence and request for reprints to: Toshitsugu Sugimoto, Third Division, Department of Medicine, Kobe University School of Medicine, 7-chome, Kusunoki-cho, Chuo-ku, Kobe 650, Japan.

Abstract

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, 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. (Endocrinology 118: 1808–1813, 1986)

Footnotes

^* This work was supported in part by Grant in Aid for Fundamental Scientific Research in 1983.

Received June 5, 1985.