Expression of 25-hydroxyvitamin D-3-1 alpha-hydroxylase in the human kidney

;The secosteroid hormone 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) plays a vital role in calcium metabolism, tissue differentiation, and normal bone growth. Biosynthesis of 1,25(OH)(2)D-3 is catalyzed by the mitochondrial cy tochrome P450 enzyme 25-hydroxyvitamin D-3 1 alpha-hydroxylase (1 alpha-hyd roxylase). Although activity of this enzyme has been described in several t issues. the kidneys are recognized to be the principal site of 1,25(OH)(2)D -3 production. To date, enzyme activity studies using vitamin D-deficient a nimals have suggested that 1 alpha-hydroxylase is expressed exclusively in proximal convoluted tubules. With the recent cloning of 1 alpha-hydroxylase , specific cRNA probes and in-house polyclonal antiserum have been used to determine the distribution of 1 alpha-hydroxylase along the human nephron. Immunohistochemistry and in situ hybridization studies indicated strong exp ression of 1 alpha-hydroxylase protein and mRNA in the distal convoluted tu bule, the cortical and medullary part of the collecting ducts, and the papi llary epithelia. Lower expression was observed along the thick ascending li mb of the loop of Henle and Bowman's capsule. Weaker and more variable expr ession of 1 alpha-hydroxylase protein and mRNA was seen in proximal convolu ted tubules, and no expression was observed in glomeruli or vascular struct ures. These data show for the first time the distribution of 1 alpha-hydrox ylase expression in normal human kidney. In contrast to earlier enzyme acti vity studies conducted in vitamin D-deficient animals, our data indicate th at the distal nephron is the predominant site of 1 alpha-hydroxylase expres sion under conditions of vitamin D sufficiency.