Developmental changes of glucocorticoid receptors in the rat pancreas

Abstract

Glucocorticoids are known to play a role in the maturation of the exocrine pancreas. The exact mechanism of glucocorticoid action in pancreatic ontogeny is, however, not clear. The present study characterized and quantitated the binding of [ 3]dexamethasone to cytosol fractions from pancreata of rats at various ages. Trunk blood samples from these rats were also checked for levels of free and bound corticosterone. Specific and saturable bindings for dexamethasone were found in pancreatic cytosol fractions from newborn suckling and adult rats. Competition studies showed a preference for steroids with glucocorticoid activity. Specific binding was relatively low in pancreatic cytosol from newly born and 1-day old pups. A significant rise was seen after day 15. Cytosolic binding capacities were greatest from pancreata obtained from pups at weaning (3rd to 5th weeks). Values then declined toward the adult level. Scatchard analysis revealed a single class of binding sites with a dissociation constant ( K d ) of 7.3 (±1.1)x 10 −8M and number of binding sites equalled to 1.29 (±0.18) × 10 −13mole/mg of cytosolic protein in adult rat pancreas. Pancreata from 25- and 15-day old rats had K d s of 3.4 (±0.8) × 10 −8M and 2.7 (±0.7) × 10 −8 M with the number of binding sites equal to 1.77 (±0.21) × 10 −13 mole/mg protein and 1.31 (±0.16) × 10 −13mole/mg protein respectively. Total plasma corticosterone concentration was low before day 10. It rose significantly by day 15, peaked at day 25, and then declined after weaning. About 5–15% of corticosterone during weaning and about 20–30% before and after weaning were in the free form. The peak level of dexamethasone binding corresponded to an increase in the plasma corticosterone level during weaning. This suggests a close relationship between plasma corticosterone levels and pancreatic glucocorticoid receptors. Both may, therefore, play a role in pancreatic development in the rat.