Hydroxylation of 25-Hydroxyvitamin D3 by Renal Mitochondria from Rats of Different Ages*

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Abstract
The hydroxylation of 25-hydroxyvitamin D3 (25OHD3) in kidney mitochondria from female rats of different ages was studied. The specific activity of 1α-hydroxylase was highest in mitochondria isolated from the 2-month-old rat (0.47 pmol/10 minmg protein), falling gradually with age to 0.17, 0.10, 0.07, and 0.06 pmol/10 minmg protein in 6-, 12-, 18-, and 24-month-old rats, respectively. The alteration in la-hydroxylase activity with age was due to a change in the V'm of the system; the K’m for 25OHD3 was unchanged (3.9–4.0 μM). The specific activity of 24-hydroxylase was lowest in mitochondria isolated from the 2-month-old rat (8.2 pmol/10 min · mg protein), increasing to 37.8, 37.4, 38.2, and 55.7 pmol/10 minmg protein in 6-, 12-, 18-, and 24-month-old rats, respectively. The alteration in 24-hydroxylase activity with age was due to a change in the V’m of the system; the K’m value for 25OHD3 was unchanged (1.1–1.2 μM). The age-dependent decrease in 1α-hydroxylase and concomitant increase in 24-hydroxylase activities observed in mitochondria isolated from kidneys of 2-, 6-, 12-, 18-, and 24-month-old rats could not be attributed to changes in the bioenergetic properties, i.e. the respiratory chain, of the mitochondria. The relative mitochondrial content of the kidney, however, probably decreased with age. These findings support the view that the kidneys of aged rats produce less 1,25-dihydroxyvitamin D3 because of lower mitochondrial 1α-hydroxylase specific activity and reduced number of mitochondria. This would be consistent with the lower levels of vitamin D hormone reported in the serum of senescent rats. (Endocrinology121: 443–448,1987)