Limited information is available on the ontogenic development of XOR and AOX, except that both enzymes are expressed in fetal tissues at levels similar to those found in adults. Regarding tissue distribution, most studies on XOR have been conducted in experimental animals rather than humans. In rodents the highest expression levels of mRNA and protein of XOR are observed in the liver, lung, kidney, and in the epithelial lining of the duodenum on the proximal side of the small intestine, decreasing steadily towards the distal portion of the small intestine. Similar expression patterns in the intestine have also been reported in humans. The mouse lung also expresses XOR, in contrast to human lung, where the enzyme is barely detectable. Other studies have also reported expression of XOR in the human brain and heart. Intracellularly, XOR is almost always localized exclusively to the cytoplasm. Interestingly, intact XOR is found in milk and other body fluids, including blood.
Tissue expression of AOX is highly variable across species, with high hepatic concentrations present in rabbit and baboon, and low concentrations found in rat and dog liver. In humans, high concentrations are found in the liver and the enzyme has also been detected immunohistochemically in respiratory, urogenital, endocrine, and digestive tissues.66 In these latter studies AOX was most abundant in the epithelial cells of the trachea and bronchium in addition to the alveolar cells of the respiratory system. In the digestive system, AOX is found in the surface epithelia of the small and large intestines. In the kidney, the proximal, distal, and collecting tubes but not the glomerulus expressed AOR. In mice, AOR exhibits gender differences where it is expressed at higher levels in males.60 It has been proposed that AOX is induced by high levels of testosterone but this induction is tissue-specific as no gender differences in the levels of XOR were observed in mice lung. No gender differences in expression have been demonstrated in humans.60
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