PTH increases renal 25(OH)D3-1α-hydroxylase (CYP1α) mRNA but not renal 1,25(OH)2D3production in adult rats

Abstract

The capacity of parathyroid hormone (PTH) to stimulate renal 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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 CYP1α, the cytochrome P-450 component of the 25(OH)D3-1α-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 CYP1α mRNA levels were measured by ribonuclease protection assay. In young rats, PTH markedly increased plasma 1,25(OH)2D3 and renal 1,25(OH)2D3 production. However, in adult rats, the response to PTH was less than 30% of that seen in young rats. Renal CYP1α 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 CYP1α 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)2D3 production in adult rats is not due to decreased induction of CYP1α mRNA.