Coexpression of mineralocorticoid receptors and 11beta-hydroxysteroid dehydrogenase 2 in human gastric mucosa.
The role of mineralocorticoids in human gastrointestinal tract is well established. In the stomach, aldosterone is thought to regulate electrolyte transport associated with gastric acid secretion. In mineralocorticoid target organs, the action of the glucocorticoid inactivating enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) facilitates aldosterone binding to a nonselective mineralocorticoid receptor (MR) in the face of high levels of circulating glucocorticoids. In the present study, we examined 25 specimens of human stomach for the presence of MR and 11beta-HSD2 using a [3H]aldosterone binding assay, Northern blot analysis, RT-PCR, and immunohistochemistry. Specific [3H]aldosterone binding sites were detected in gastric fundic mucosa, but not in the antrum. In fundic mucosa the Kd was 0.72+/-0.05 nmol/L (mean +/- SE), and Bmax was 6.0+/-1.4 fmol per milligram of protein. Northern blot analysis demonstrated a faint band for MR mRNA at 6.0 kb, although message for 11beta-HSD2 was undetectable. However, RT-PCR demonstrated specific PCR products for both MR and 11beta-HSD2. Immunohistochemistry demonstrated the colocalization of MR and 11beta-HSD2 only in parietal cells. MR-positive cells were further characterized by electron microscopy, confirming the identity of parietal cells. This study shows that parietal cells contain both MR and 11beta-HSD2, suggesting that the human stomach is a novel target organ for mineralocorticoids. Aldosterone may, therefore, regulate biological functions of parietal cells including gastric acid secretion.
Kato
K
K
The Department of Medicine III, Tohoku University School of Medicine, Sendai, Japan. kato-ka@mx2.nisiq.net
Sasano
H
H
Ohara
S
S
Sekine
H
H
Mochizuki
S
S
Mune
T
T
Yasuda
K
K
Nagura
H
H
Shimosegawa
T
T
Toyota
T
T
Krozowski
Z
Z
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000378:metabolism; D015152:Blotting, Northern; D005748:Gastric Fundus / Q000737:chemistry / Q000378:metabolism; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000032:analysis; D018161:Receptors, Mineralocorticoid / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism; D014316:Tritium
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D014316:Tritium; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases