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 pe psinogen in the adult rat stomach. This decrease was mainly due to a r eduction in the level of the main component of rat pepsinogen isozymog ens, namely, Pgl and in the level of expression of Pgl mRNA, with a ma ximal effect being evident 48 hours after operation. Immunohistochemic al analysis revealed that the level of expression of Pgl in the pepsin ogen-producing cells was decreased throughout the stomach mucosa and t his decrease was especially marked in the immature chief cells located in the glandular neck of the fundic mucosa. Adrenalectomy also increa sed the proliferation of mucosal cells and suppressed the expression o f cathepsin E and class m mucin, markers of differentiated stomach muc osa. All these changes were reversed by hydrocortisone replacement and the extent of the recovery of the level of Pgl mRNA was dependent on the dose of hydrocortisone, indicating the transcriptional control of the Pgl gene by hydrocortisone. The observed results suggest that the continuous presence of glucocorticoids is necessary for active transcr iption of Pgl gene in fully differentiated stomach mucosa and that glu cocorticoids are important regulators of both the function and the mor phology of stomach mucosal cells. (C) 1994 Academic Press, Inc.