Glucocorticoids inhibit the proliferation of mucosal cells and enhance the expression of a gene for pepsinogen and other markers of differentiation in the stomach mucosa of the adult rat.
Adrenalectomy caused a significant decrease in the mucosal level of pepsinogen in the adult rat stomach. This decrease was mainly due to a reduction in the level of the main component of rat pepsinogen isozymogens, namely, Pg1 and in the level of expression of Pg1 mRNA, with a maximal effect being evident 48 hours after operation. Immunohistochemical analysis revealed that the level of expression of Pg1 in the pepsinogen-producing cells was decreased throughout the stomach mucosa and this decrease was especially marked in the immature chief cells located in the glandular neck of the fundic mucosa. Adrenalectomy also increased the proliferation of mucosal cells and suppressed the expression of cathepsin E and class III mucin, markers of differentiated stomach mucosa. All these changes were reversed by hydrocortisone replacement and the extent of the recovery of the level of Pg1 mRNA was dependent on the dose of hydrocortisone, indicating the transcriptional control of the Pg1 gene by hydrocortisone. The observed results suggest that the continuous presence of glucocorticoids is necessary for active transcription of Pg1 gene in fully differentiated stomach mucosa and that glucocorticoids are important regulators of both the function and the morphology of stomach mucosal cells.
1st Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
S
S
Tsukada
M
M
Ichinose
M
M
Tatematsu
N
N
Tezuka
S
S
Yonezawa
N
N
Kakei
M
M
Matsushima
K
K
Miki
K
K
Kurokawa
T
T
Kageyama
D000315:Adrenalectomy; D000818:Animals; D015415:Biomarkers; D020059:Cathepsin E; D002403:Cathepsins / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015870:Gene Expression / Q000187:drug effects*; D006854:Hydrocortisone / Q000031:analogs & derivatives* / Q000494:pharmacology; D007124:Immunoenzyme Techniques; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis / Q000096:biosynthesis / Q000302:isolation & purification; D008297:Male; D010435:Pepsinogens / Q000032:analysis / Q000096:biosynthesis* / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar
D015415:Biomarkers; D007527:Isoenzymes; D010435:Pepsinogens; D002403:Cathepsins; D020059:Cathepsin E; C007133:hydrocortisone hemisuccinate; D006854:Hydrocortisone