Aldosterone enhances 11beta-hydroxysteroid dehydrogenase type 2 expression in colonic epithelial cells in vivo.
OBJECTIVE
[corrected] 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) metabolizes glucocorticoids, thus enabling aldosterone to bind to the mineralocorticoid receptor. However, little is known about the regulatory mechanism of epithelial 11beta-HSD2 expression in the gut.


METHODS
Sprague-Dawley rats were maintained on a sodium-depleted diet or subjected to continuous aldosterone infusion for 4 weeks. Plasma aldosterone and arginine-vasopressin (AVP) levels were measured by radioimmunoassay. Expression of 11beta-HSD2 in colonic epithelia was evaluated by Northern blotting and immunohistochemistry. T84 and Caco2 cells were stimulated with aldosterone, dexamethasone and AVP alone or in combination, and 11beta-HSD2 mRNA was measured by quantitative reverse transcription polymerase chain reaction (RT-PCR).


RESULTS
Sodium-depleted and aldosterone-infused rats showed an increase of plasma aldosterone and AVP. Both treatments resulted in induction of 11beta-HSD2 in the colonic epithelia at mRNA and protein levels. Positive immunoreactivity was detected in the cytoplasm of the surface epithelia in control rats. In contrast, epithelial cells in the crypt also showed immunoreactivity for 11beta-HSD2 in the proximal colon of dietary sodium-depleted and aldosterone-infused rats. Induction of 11beta-HSD2 mRNA was observed when T84 cells were stimulated with corticosteroids plus AVP.


CONCLUSIONS
Aldosterone has a pivotal role by increasing expression of 11beta-HSD2 in epithelial cells of the colon. AVP may act as a synergistic hormone in aldosterone-mediated 11beta-HSD2 induction.
Fukushima
Kouhei
K
Department of Surgery, Tohoku University, Graduate School of Medicine, Sendai, Japan. kouhei@surg1.med.tohoku.ac.jp
Funayama
Yuji
Y
Yonezawa
Hitoshi
H
Takahashi
Kenichi
K
Haneda
Sho
S
Suzuki
Takashi
T
Sasano
Hironobu
H
Naito
Hiroo
H
Shibata
Chikashi
C
Krozowski
Zygmunt S
ZS
Sasaki
Iwao
I
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000187:drug effects* / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001707:Biopsy, Needle; D015152:Blotting, Northern; D002478:Cells, Cultured; D003106:Colon / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism / Q000473:pathology; D008297:Male; D008969:Molecular Sequence Data; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012680:Sensitivity and Specificity; D012964:Sodium / Q000172:deficiency
D012333:RNA, Messenger; D000450:Aldosterone; D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2