17β-hydroxysteroid dehydrogenase type 2 expression and enzyme activity in the human gastrointestinal tract

The 17β-hydroxysteroid dehydrogenases (17βHSDs) play an important role in the regulation of intracellular levels of biologically active sex steroid hormones in various human tissues. To date, eight distinctive 17βHSD enzymes have been cloned and characterized in humans. Among these isoenzymes, 17βHSD type 2 (17βHSD2) catalyses the conversion of testosterone into androstenedione and/or oestradiol into oestrone in various tissues, and it has thus been suggested to be involved in the biological inactivation of these sex steroids. The human gastrointestinal tract and liver are considered as the principle sites of inactivation and metabolism of various forms of orally administered sex steroids. We therefore examined 17βHSD2 expression and activity in human adult non-pathological gastrointestinal tract in order to clarify further the biological significance of this enzyme. A total of 80 specimens (40 from males and 40 from females) of normal oesophageal, stomach, duodenal, ileal, colonic and rectal tissues were examined for immunohistochemistry. Altogether, 17 tissue specimens were used for enzyme assay, and eight for RNA analysis. 17βHSD2 activity was detected in the stomach, duodenum, ileum, colon and rectum. 17βHSD2 mRNA was most abundant in the small intestine. 17βHSD2 immunoreactivity was localized almost exclusively to the absorptive epithelium, which may be involved in the inactivation of excessive endogenous and exogenous active sex steroids. Results from the present study thus suggest that the human gastrointestinal tract is an important sex steroid metabolizing organ in humans.