The Effect of Cholecystokinin-Octapeptide, Insulin, Glucagon, Triiodothyronine, and Epidermal Growth Factor on Amylase Activity in Fetal Pancreas in Vitro

Abstract

ABSTRAm. To evaluate the possible role of various hormones on fetal pancreas development, late gestational fetal rat pancreata (20 days) were cultured in a serum-free medium for 6 days in the presence of cholecystokininoctapeptide (CCK-8), epidermal growth factor, triiodothyronine, or glucagon with or without dexamethasone. In the absence of any added hormone, the tissue amylase activity declined very rapidly. Epidermal growth factor alone (4. M) could not preserve the amylase activity, whereas triiodothyronine (0.1 pM) and glucagon (4 pglml) had a deleterious effect that was prevented by the addition of DXM (3. M). In the presence of CCK-8 (2. lo-" M) 50 and 30% of the amylase activity was maintained on the 2nd and the 4th day of culture, respectively. The CCK-8 effect was dose dependent and was inhibited by asperlicin (10 pM). The combination of CCK-8 and dexamethasone maintained more than 80% of the amylase activity in the fetal pancreas explants through 4 days of culture. Fetal pancreas cultured in this optimal medium and treated with streptozotocin (lo-' M) during the 1st day of culture showed a significantly lower tissue amylase activity on the 4th and 6th days than those not treated with streptozotocin. The streptozotocin effect was attenuated when insulin (0.1 U/ml) was added. These data suggest that, in addition to the well-known effect of glucocorticoid on enzyme activities in the fetal pancreas, two additional hormones, CCK and insulin, could play a role in the modulation of pancreatic amylase activity in the fetal rat. (Pediatr Res 23: 539-542, 1988 Abbreviations CCK, cholecystokinin EGF, epidermal growth factor DXM, dexamethasone SFM, serum-free medium BSA, bovine serum albumin CCK-8, CCK-octapeptide T3, triiodothyronine ASA, amylase-specific activityIn the rat, the development of the exocrine pancreatic enzymes has been shown to be a three-phase process (1). The primary transition (day 10 of gestation) leads to the accumulation of very low specific activities of exocrine enzymes without any zymogen granules. Then, according with the appearance of the granules, the activities of exocrine enzymes start to increase dramatically at day 15 of gestation. Finally, shortly after birth, the third phase leads to a decrease of most of the enzymes. The role of hormones in these perinatal changes was first suggested by the fact that the pancreatic mass of newborn rats was decreased by decapitation in utero (2). In vivo experiments have shown that hydrocortisone and CCK increased the amylase-specific activity in the term fetal pancreas (3-3, whereas thyroxine and glucagon did not modulate this enzyme at the same developmental stage (3). These in vivo studies have several disadvantages, i.e. the effect of the placental bamer and the possible complication of mother-fetus interaction during the experiments. To bypass these pitfalls, several groups developed in vitro models that enabled them to show that corticosteroids (but not gonadal steroids) increased the amount of enzymes in cultured fetal pancreata but di...

Gut Regulatory Peptide Levels in Bovine Fetuses and Their Dams between the 3rd and 9th Months of Gestation

“…Gastrin and somatostatin extracted from fetal gastric tissue in rabbits modify parietal cell activity [48]. CCK was shown to stimulate amylase secretion in fetal rat pancreatic cells [27]. Taken together, these diverse observations suggest that fetal endocrine cells release their secretory products in a regulated manner, and that peptides are capable to interfere with functional targets.…”