In VivoEvidence for the Intermediary Role of 3′,5′-Cyclic AMP in Parathyroid Hormone-Induced Stimulation of lα,25-Dihydroxy vitamin D3Synthesis in Rats

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Abstract
The stimulatory effect of parathyroid hormone (PTH) on renal 1.alpha.-hydroxylation of 25-hydroxyvitamin D3 (25-OH-D3) was studied in thyroparathyroidectomized (TPTX), vitamin D-deficient rats into which bovine PTH, theophylline, c[cyclic]AMP or dibutyryl cAMP (dbcAMP) was constantly infused. The accumulation in plasma of 1.alpha.,25-dihydroxyvitamin D3 [1.alpha.,25-(OH)2-D3], produced from 25-OH-D3, was enhanced by infusion of either cAMP (0.9 .mu.mol/h) or dbcAMP (1 .mu.mol/h) to a level similar to the maximum obtained by PTH (2.5-7.5 U/h) infusion. A submaximal dose (1 U[unit]/h) of PTH caused a similar extent of stimulation, when infused with theophylline. When either 2 .mu.mol/h of cAMP or 7.5 U/h of bovine PTH was infused starting 18 h after TPTX, the accumulation of 1.alpha.,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 1.alpha.,25-(OH)2-D3 production induced by both exogenous and endogenous PTH.