25-Hydroxycholecalciferol Metabolism in Hypophysectomized Rats*

Abstract

The metabolism of 25-hydroxycholecalciferol (25-(OH)D3) was investigated in vitamin D normal rats, 4 wk after hypophysectomy. Compared to sham-operated controls, these animals were hypophosphatemic, and their parathyroid glands were significantly smaller than normal. Eighteen hours after i.p. injection of a single dose of 3H 25-(OH)D3 (50 pmol), chromatography of serum extracts on Sephadex LH-20 and high pressure liquid chromatography showed that the percentage of radioactivity corresponding to 24,25-dihydroxycholecalciferol [24,25-(OH)2D3] was significantly higher in hypophysectomized rats (11.7 .+-. 0.95% vs. 6.9 .+-. 0.78%). No radioactivity was detected in the area corresponding to 1,25-dihydroxycholecalciferol. In hypophysectomized rats injected 2 wk with radioactive 25-(OH)D3, the amount of 24,25(OH)2D3 was still higher than in sham-operated controls. Parathyroidectomy 48 h before the injection of [3H]25(OH)D3 abolished the difference between the 2 groups. The percentage of 24,25-(OH)2D3 in the serum of hypophysectomized rats could be decreased to sham-operated control level by repeated administration of parathormone or 2 injections of bovine GH. The effect of GH administration was less marked in hypophysectomized-parathyroidectomized animals. These results demonstrate that the conversion of 25-(OH)D3 to its 24-hydroxylated metabolite is increased in hypophysectomized rats fed a normal Ca, normal P, vitamin D-supplemented diet. They also suggest that this change in 25-(OH)D3 metabolism is either directly or indirectly related to the lack of GH.