Effects of parathyroid hormone and vitamin D on the renal vitamin K-dependent carboxylating system

The vitamin K-dependent production of gamma-carboxyglutamic acid-containing protein occurs in the kidney. This protein, which we will call KGP, has no assigned physiological role. In the experiments described here, the effects of the calcium-regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), on the renal vitamin K-dependent carboxylation system were studied. PTH, when administered via continuous infusion at 3 units/h using a subcutaneous osmotic pump, caused a time-dependent increase in the activity of the renal gamma-glutamyl carboxylase which was detectable after 2 days and continued to increase up to day 7 of infusion. The increase was more marked in thyroparathyroidectomized rats than in intact rats, suggesting the possibility of an antagonistic action by endogenous calcitonin. Treatment of intact rats with 1,25-(OH)2D3 by daily intraperitoneal injections also caused a time-dependent increase in the activity of the carboxylase. When the warfarin-mediated accrual in renal microsomes of the precursor of KGP was measured, treatment with either parathyroid hormone plus warfarin or 1,25-(OH)2D3 plus warfarin caused a significant increase in precursor relative to animals treated with warfarin alone. Thus, the synthesis of KGP is modulated by these two calcium regulating hormones both by increasing the synthesis of KGP precursor as well as by increasing the activity of the carboxylase enzyme which catalyzes post-translational modification of the precursor.