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11ß-Hydroxysteroid Dehydrogenase Type 2 and Mineralocorticoid Receptor in Human Fetal Development

Departments of Pathology (G.H., H.S., T.S., J.T., Y.M., H.N.), Internal Medicine (G.H., N.H., T.T.), and Surgery (K.F.), Tohoku University School of Medicine, Sendai, Japan; and the Laboratory of Molecular Hypertension, Baker Medical Research Institute (Z.S.K.), Melbourne, Australia

Address all correspondence and requests for reprints to: Gen Hirasawa, M.D., Department of Pathology, Tohoku University School of Medicine, 2–1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. E-mail: g-hirasawa{at}patholo2.med.tohoku.ac.jp

11ß-Hydroxysteroid dehydrogenase type II (11ßHSD2) confers specificity on the mineralocorticoid receptor (MR) by converting biologically active glucocorticoids to inactive 11-keto metabolites. The biological significance of 11ßHSD2 activity during fetal development is currently being explored, but the temporal and spatial distributions of the enzyme and receptor have not been examined. We therefore examined their distributions during various stages of human fetal development using immunohistochemistry. Both 11ßHSD2 and MR immunoreactivity were detected in the distal convoluted and collecting tubules of the kidney from early in gestation. Fetal skin, intermediate layer of the epidermis, peridermal cells, and hair follicles were positive for both 11ßHSD2 and MR. Weak 11ßHSD2 and MR immunoreactivity was detected in the superficial ciliated epithelium of the esophagus, the deep layer of gastric epithelial cells, and the superficial epithelium of the small intestine. Columnar epithelium in the terminal bronchiolar budding component of fetal lung and tracheal and bronchial ciliated epithelium were also positive for MR and 11ßHSD2 from early gestation. Colonic epithelium and pancreatic exocrine duct cells, which demonstrated marked immunoreactivity of both MR and 11ßHSD2 in the adult, did not express MR and 11ßHSD2 until very late in gestation. These results imply that mineralocorticoid action in the upper fetal gastrointestinal tract, kidney, skin, and lung is facilitated by 11ßHSD2 and is involved in water and electrolyte transport between fetus and amniotic fluid as well as fetal urine production.

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