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The vitamin D hormone 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) is generated by a series of hydroxylation steps in the liver and kidneys. We investigated whether naturally vitamin D-deficient subterranean mammals (naked mole rats, Heterocephalus glaber) employ the same enzymatic pathways, and whether these are regulated in a similar manner to that established for other mammals.

Vitamin D₃-25-hydroxylase in the liver and both 25-hydroxyvitamin D₃-l-hydroxylase and 25-hydroxyvitamin D₃-24 hydroxylase (1-OHase and 24-OHase) in the kidney were detectable in mole rats. As expected for vitamin D-deficient mammals, the 1-OHase activity predominated over the 24-OHase. After mole rats received a supraphysiological supplement of vitamin D₃, 1-OHase activity was suppressed and 24-OHase activity was enhanced. Irrespective of vitamin D status, forskolin (a protein kinase A activator) and dibutyryl cyclic AMP did not alter the activity of either 1-OHase or 24-OHase. These findings suggest that the response of renal hydroxylases to parathyroid hormone was blunted. Phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) (protein kinase C activators), suppressed 1-OHase activity. 24-OHase activity was induced by TPA but not by OAG. These effects were similar to those illicited by vitamin D₃ supplementation but were additive in that they increased the responses shown in vitamin D-replete mole rats.

These data confirm that naturally vitamin D-deficient mole rats can convert vitamin D₃ to the hormone, 1,25(OH)₂D₃. Furthermore, the enzymes 1-OHase and 24-OHase present in the kidneys of these mammals are regulated independently by 1,25(OH)₂D₃ and protein kinase C-mediated pathways of intracellular signalling, but are not regulated by the cyclic AMP–protein kinase A signal transduction pathway.

Journal of Endocrinology (1993) 138, 59–64