11ß-Hydroxysteroid Dehydrogenase Type 2 and Mineralocorticoid Receptor in Human Fetal Development
Gen Hirasawa,
Hironobu Sasano,
Takashi Suzuki,
Junji Takeyama,
Yasunari Muramatu,
Kouhei Fukushima,
Nobuo Hiwatashi,
Takayoshi Toyota,
Hiroshi Nagura and
Zygmunt S. Krozowski
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) byconverting
biologically active glucocorticoids to inactive 11-ketometabolites.
The biological significance of 11ßHSD2 activityduring fetal
development is currently being explored, but thetemporal and spatial
distributions of the enzyme and receptorhave not been examined. We
therefore examined their distributionsduring various stages of human
fetal development using immunohistochemistry.Both 11ßHSD2 and MR
immunoreactivity were detected inthe distal convoluted and collecting
tubules of the kidney fromearly in gestation. Fetal skin, intermediate
layer of the epidermis,peridermal cells, and hair follicles were
positive for both11ßHSD2 and MR. Weak 11ßHSD2 and MR
immunoreactivitywas detected in the superficial ciliated epithelium of
the esophagus,the deep layer of gastric epithelial cells, and the
superficialepithelium of the small intestine. Columnar epithelium in
theterminal bronchiolar budding component of fetal lung and tracheal
andbronchial ciliated epithelium were also positive for MR and
11ßHSD2from early gestation. Colonic epithelium and pancreatic
exocrineduct cells, which demonstrated marked immunoreactivity of both
MRand 11ßHSD2 in the adult, did not express MR and 11ßHSD2until
very late in gestation. These results imply that mineralocorticoid
actionin the upper fetal gastrointestinal tract, kidney, skin, and
lungis facilitated by 11ßHSD2 and is involved in water and
electrolytetransport between fetus and amniotic fluid as well as fetal
urineproduction.
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