Control of γ-Glutamyl Transpeptidase Expression by Glucocorticoids in the Rat Pancreas

Abstract

Glucocorticoids are known to promote the formation of zymogen granules in acinar cells of the exocrine pancreas in vivo as well as in vitro. To gain insight into the mechanism of this regulation, we studied the effects of glucocorticoids on the synthesis of two components of the secretory granule membrane, the glycoprotein 2 (GP-2) and the ␥-glutamyl transpeptidase (GGT). It was demonstrated that following adrenalectomy, degranulation of pancreatic acinar cells is accompanied by a sharp decrease in GGT and GP-2 synthesis as measured by mRNA and protein accumulation. The decline of GGT synthesis was prevented by glucocorticoid replacement therapy, whereas GP-2 synthesis could be maintained with either glucocorticoid or estradiol treatment. These in vivo observations were corroborated and extended in an in vitro study using AR42J pancreatic cells. With this cell line, it was demonstrated that dexamethasone induces the formation of zymogen granules and the accumulation of a specific GGT transcript (mRNA III) by decreasing its degradation rate. At the same time, the GP-2 mRNA level was not modified by the hormonal treatment. These data demonstrate that glucocorticoids exert a positive control on the GGT expression in pancreatic cells at a post-transcriptional level. GGT, an enzyme of the glutathione metabolism, could play a significant role in protein packaging in secretory cells.

Models of exocrine pancreatic pathologies: A microscopical point of view

“…Molecular probes have indicated that the mRNAs for these three proteins GP-2, g-GT and amylase are significantly reduced in vivo after adrenalectomy. Moreover, the mRNAs for these three proteins were increased after a glucocorticoid replacement therapy (Chobert et al, 1996). Presence of laminar bodies in the acinar lumen has also been reported in reserpine treated rats (See Fig.…”

“…9d). In AR42J cells, glucocorticoid could induce regranulation and increase the mRNA levels of amylase and g-GT (Chobert et al, 1996). These cells also possessed estradiol receptors (Beaudoin et al, 1991), but in contrast to normal pancreas in vivo, there was no increase in g-GT mRNA or regranulation after exposure to glucocorticoid.…”

“…Glucocorticoids also regulate the synthesis of g-GT, a zymogen granule membrane glycoprotein in the same cells. These regulations at different sites of the secretory apparatus indicate a well integrated effect of glucocorticoids on the secretory apparatus (Chobert et al, 1996).…”

Changes in the glutathione system of lung cell lines after treatment with hydrocortisone

“…GCs are known to increase GSH levels in some cells, e.g. hepatocytes, HeLa cells, fibroblasts, or renal tubular cells (Cai et al 1995(Cai et al , 1997Chobert et al 1996;Lu et al 1992;Millar and Jinks 1985;Wolff et al 1996). Therefore, it was surprising to find a decrease in GSH content of the alveolar epithelial cells in this study.…”

Expression of pro-Muclin in pancreatic AR42J cells induces functional regulated secretory granules

“…The effects of dexamethasone on the AR42J cell are complex. Dexamethasone increases mRNA transcription for some RSPs (27), increases message stability for others (8), and can enhance protein translation (26). There is also an increase in rough endoplasmic reticulum (27) that is due to a structural reorganization of the protein translation machinery (32).…”