EFFECTS OF 19-NOR-1,25(OH)(2)D-2, A NEW ANALOG OF CALCITRIOL, ON SECONDARY HYPERPARATHYROIDISM IN UREMIC RATS

The active metabolite of vitamin D, calcitriol [1,25(OH)(2)D-3] suppre sses parathyroid hormone (PTH) gene transcription and PTH secretion. A lthough 1,25(OH)(2)D-3 is effective in suppressing secondary hyperpara thyroidism in uremic patients, the mandatory use of large amounts of c alcium salts to control serum phosphorus may preclude in some patients the use of ideal therapeutic doses of 1,25(OH)(2)D-3 because of hyper calcemia. We have studied a new analogue of calcitriol, 19-nor-1,25(OH )(2)D-2 that possesses low calcemic and phosphatemic activity. We have clearly demonstrated that this analogue of calcitriol can suppress se condary hyperparathyroidism without inducing hypercalcemia or hyperpho sphatemia in uremic rats. In addition, this analogue of vitamin D supr esses pre-pro PTH messenger RNA in a similar fashion to that of 1,25(O H)(2)D-3. Contrary to the effect of 1,25(OH)2D3 that increases the int estinal vitamin D receptor, this analogue of vitamin D suppresses the intestinal vitamin D receptor. This finding may be critical for the la ck of calcemic activity of 19-nor-1,25(OH)(2)D-2 seen in these studies . One of the explanations for the lack of an increasing intestinal VDR is the fact that 19-nor-1,25(OH)(2)D-2 decreases endogenous levels of 1,25(OH)(2)D-3. In summary, we have shown that 19-nor-1,25(OH)(2)D-2, a new analogue of calcitriol is effective in suppressing PTH in uremi c rats with secondary hyperparathyroidism. In addition, there is a sig nificant decrease in the VDR in the intestine, which may explain in pa rt the less calcemic and hyperphosphatemic effect of this analogue. (C ) 1998 by the National Kidney Foundation, Inc.