PTH increases renal 25(OH)D3-1α-hydroxylase (CYP1α) mRNA but not renal 1,25(OH)2D3 production in adult rats

The capacity of parathyroid hormone ( PTH) to stimulate renal 1,25- dihydroxyvitamin D-3 [ 1,25( OH) D-2(3)] production declines with age in the rat. The purpose of these studies was to determine whether this decline is due to a decreased capacity of PTH to increase the mRNA levels of CYP1alpha, the cytochrome P- 450 component of the 25( OH)D-3- 1alpha- hydroxylase. Young ( 2 mo) and adult ( 12 mo) male Fischer 344 rats were parathyroidectomized ( PTX). After 72 h, PTX rats were injected with PTH or vehicle at 24, 6, and 3 h before death, and renal CYP1alpha mRNA levels were measured by ribonuclease protection assay. In young rats, PTH markedly increased plasma 1,25( OH) D-2(3) and renal 1,25( OH) D-2(3) production. However, in adult rats, the response to PTH was less than 30% of that seen in young rats. Renal CYP1alpha mRNA levels, on the other hand, were increased over fivefold by PTH in both young and adult rats. In in vitro studies, PTH/ forskolin increased CYP1alpha mRNA levels over twofold in renal slices from both young and adult PTX rats. These studies demonstrate that the decreased capacity of PTH to increase 1,25( OH) D-2(3) production in adult rats is not due to decreased induction of CYP1alpha mRNA.