Steroids and the Secretory Function of the Exocrine Pancreas*

Abstract

The influence of steroids on the exocrine pancreas of male rats was examined by removing steroid producing tissue and by introducing individual steroids into these animals at a later date. Castration had no demonstrable morphological effect on acinar cells, whereas castration combined with adrenalectomy caused a marked depletion of zymogen granules as well as widening of peri- and interlobular spaces. Treatment of castrated-adrenalectomized rats with estradiol restored a normal appearance of the pancreas within about 9 h. Triamcinolone acetonide produced similar results. These morphological changes were accompanied by significant alterations of the relative amounts of digestive enzymes present in zymogen granules. A marked reduction of amylase occurred in the castrated-adrenalectomized group. Neither estradiol nor triamcinolone could reverse these effects within 9 h. Castration alone had no significant effect on the relative proportion of amylase; however, it increased the relative amount of proteases. This effect was reversed by estradiol treatment. Estradiol also induced significant changes in the proportion of proelastase in castrated-adrenalectomized animals. Replacement therapy in castrated-adrenalectomized rats with dexamethasone or triamcinolone partially restored the level of amylase in the pancreas, whereas estradiol did not cause any significant effect. At the ultrastructural level, castration and adrenalectomy caused swelling of the Golgi apparatus and accumulation of condensing vacuoles. These effects were reversed by either estradiol or triamcinolone. Also, after acute treatment of these animals with estradiol, two unusual features of acini were noted. In some acini, a type of granule that we termed halo granule appeared. These halo granules were either distinctly separated organelles or formed composite structures that did not appear to be associated with the luminal membrane. Freeze-fracture studies revealed that secretory vesicles in apparently normal acini adhered to each other at specific contact sites characterized by aggregates of intramembrane particles. Multiple sites of contact could be seen in the same vesicle. From our observations it is clear that steroids from the testes and adrenals exert major effects on the secretory apparatus of pancreas; more specifically on the mechanisms that determine the proportions of the different digestive enzyme and on their packaging in the zymogen granules.

Immunocytochemical localization of gamma-glutamyltranspeptidase, GP-2 and amylase in the rat exocrine pancreas: the concept of zymogen granule membrane recycling after exocytosis.

“…This is indicated by a good correlation between GGT and digestive enzyme outputs during stimulation (2). An alternative mechanism is that the newly added ZG membrane, bearing GGT, mixes with the apical membrane and is subsequently shed when microvilli fragment into pancreasomes in the lumen (6). These mechanisms are not mutually exclusive and probably operate concomitantly.…”

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

“…Electron Microscopy-Cell pellets and pieces of pancreas tissues were processed for electron microscopy as described previously (4).…”

“…Possible clues for the elucidation of these processes come from experiments which reported that adrenalectomy of male rats caused a marked depletion of ZG in the pancreas acinar cells, an effect which was reversed by treatment with the synthetic glucocorticoid, triamcinolone (3,4). It was also found that a dexamethasone treatment of the AR42J rat pancreatic cells induces the appearance of ZG (5).…”

“…This implies a de novo synthesis of these proteins and their insertion into the recycled membrane as new granules form. If these proteins are essential for protein packaging and ZG formation, therefore, one could postulate an increase in their rate of synthesis when ZG formation is induced by glucocorticoids (4).…”

Estradiol Has a Direct Impact on the Exocrine Pancreas as Demonstrated by Enzyme and Vigilin Expression

“…In mammals as well, the pancreas binds gonadal hormones, and absorbs more sexual steroid hormones than classical target tissues such as the prostate gland [1]. Boctor et al [2] detected specific estradiol-binding proteins in the pancreas of rats and Beaudoin et al [3] demonstrated estradiol-induced changes in both the enzyme secretion and the pancreas histology (indicating reduced secretion). Previous evidence that estradiol had a stimulatory effect on cellular trypsinogen production in fish [4] as well as the presence of estradiol receptors in the exocrine pancreas [5] led us to investigate the effect of estradiol on pancreatic cells.…”