Extrarenal expression of 25-hydroxyvitamin D-3-1 alpha-hydroxylase

The mitochondrial enzyme 25-hydroxyvitamin D-3-1 alpha -hydroxylase (1 alph a -hydroxylase) plays an important role in calcium homeostasis by catalyzin g synthesis of the active form of vitamin D, 1,25-dihydroxyvitamin D-3, in the kidney. However, enzyme activity assays indicate that 1 alpha -hydroxyl ase is also expressed in a variety of extrarenal tissues; recent cloning of cDNAs for 1 alpha -hydroxylase in different species suggests that a simila r gene product is found at both renal and extrarenal sites. Using specific complementary ribonucleic acid probes and antisera to 1 alpha -hydroxylase, we have previously reported the distribution of messenger ribonucleic acid and protein for the enzyme along the mouse and human nephron. Here we desc ribe further immunohistochemical and Western blot analyses that detail for the first time the extrarenal distribution of 1 alpha -hydroxylase in both normal and diseased tissues. Specific staining for 1 alpha -hydroxylase was detected in shin (basal keratinocytes, hair follicles), lymph nodes (granu lomata), colon (epithelial cells and parasympathetic ganglia), pancreas (is lets), adrenal medulla, brain (cerebellum and cerebral cortex), and placent a (decidual and trophoblastic cells). Further studies using psoriatic skin highlighted overexpression of 1 alpha -hydroxylase throughout the dysregula ted stratum spinosum. Increased expression of skin 1 alpha -hydroxylase was also associated with sarcoidosis. In lymph nodes and skin from these patie nts 1 alpha -hydroxylase expression was observed in cells positive for the surface antigen CD68 (macrophages). The data presented here confirm the pre sence of protein for 1 alpha -hydroxylase in several extrarenal tissues, su ch as skin, placenta, and lymph nodes. The function of this enzyme at novel extrarenal sites, such as adrenal medulla, brain, pancreas, and colon, rem ains to be determined. However, the discrete patterns of staining in these tissues emphasizes a possible role for 1 alpha -hydroxylase as an intracrin e modulator of vitamin D function in peripheral tissues.