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In Vivo Evidence for the Intermediary Role of 3',5'-Cyclic AMP in Parathyroid Hormone-Induced Stimulation of l,25-Dihydroxy vitamin D₃ Synthesis in Rats

NOBORU HORIUCHI, TATSUO SUDA^*, HIROO TAKAHASHI, EIICHIRO SHIMAZAWA and ETSURO OGATA

Department of Biochemistry, School of Dentistry, Tokyo Medical and Dental University Yushima, Bunkyo-ku, Tokyo 113
Research Laboratories of Teikoku Hormone Manufacturing Co. Kawasaki 213
Department of Medicine, University of Tsukuba Ibaraki 300-31, japan

^* Address correspondence to: Tatsuo Suda, Department of Biochemistry, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan 113.

Abstract

The stimulatory effect of parathyroid hormone (PTH) on renal la-hydroxylation of 25- hydroxyvitamin D₃ (25-OH-D₃) was studied in thyroparathyroidectomized (TPTX), vitamin D-deficient rats into which bovine PTH, theophylline, cAMP or dibutyryl cAMP (dbcAMP) was constantly infused. The accumulation in plasma of 1,25-dihydroxy vitamin D₃ [1,25-(OH)_2^–D₃], produced from 25- OH-D₃, was enhanced by infusion of either cAMP (0.9 µmol/h) or dbcAMP (1 µmol/h) to a level similar to the maximum obtained by PTH (2.5-7.5 U/h) infusion. A submaximal dose (1 U/h) of PTH caused a similar extent of stimulation, when infused with theophylline. When either 2 µmol/h of cAMP or 7.5 U/h of bovine PTH was infused starting 18 h after TPTX, the accumulation of l,25-(OH)_2^–D₃ in plasma was similarly restored within 6 h to the level found in the sham-operated animals. These results strongly support the concept that cAMP plays an important intermediary role in the stimulation of l,25-(OH)_2^–D₃ production induced by both exogenous and endogenous PTH.

Footnotes

Abbreviations used: 25-OH-D₃, 25-hydroxyvitamin D₃; l,25-(OH)_2^–D₃, l,25-dihydroxyvitamin D₃; 24,25-OH)_2^–D₃, 24,25-dihydroxyvitamin D₃; PTH, parathyroid hormone; TPTX, thyroparathyroidectomy or thyroparathyroidectomized.

Received December 28, 1976.

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