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 gamma-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.
Highlights
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)
Morphological Examination—As illustrated by representative micrographs (Fig. 1, A–D), a decrease in the number of zymogen granule (ZG) was observed in the pancreatic acinar cells of adrenalectomized rats (Fig. 1B) as compared with the number found in cells from control animals (Fig. 1A)
Summary
(Received for publication, December 11, 1995, and in revised form, February 28, 1996). Biochemical and immunocytochemical observations have indicated that both GP-2 and GGT are continuously released by the pancreas acinar cell in the pancreatic juice, and, a substantial fraction of these proteins do not follow its host membrane that recycles after exocytosis [11, 12, 15]. This implies a de novo synthesis of these proteins and their insertion into the recycled membrane as new granules form. We provide evidence that ZG formation can be induced independently of GP-2 expression
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