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Autologous Regulation of Pancreatic Glucocorticoid Receptors in Suckling Rats

The exact mechanism of glucocorticoid action in pancreatic ontogeny is not fully understood. To investigate whether glucocorticoid receptors are subjected to autologous regulation during the early stage of life, the effects of glucocorticoid administration and adrenalectomy (Adx) were examined. Rat pups adrenalectomized on day 10 were given either dexamethasone (DX, 20 μg/100 g body weight) or vehicle daily for 3 days before being killed at 15 days of age. Adx increased and DX replacement decreased glucocorticoid receptor binding in the developing rat pancreas. Scatchard analysis showed that Adx led to an increase in receptor number without changing its affinity (Bmax, from 0.385 ± 0.073 to 0.553 ± 0.086 pmol/mg protein; Kd, from 2.2 ± 0.5 × 10−8 M to 2.7 ± 0.6 × 10−8M), whereas DX down-regulated its own receptor by decreasing the receptor number and lowering the affinity (Bmax, from 0.553 ± 0.086 to 0.140 ± 0.025 pmol/mg protein; Kd, from 2.7 ± 0.6 × 10−8 M to 8.8 ± 2.5 × 10−8 M). The degree of down-regulation was dependent on the dose of DX. Maximal down-regulation (80%) was found at 20 μg/100 g body weight, whereas a dose of 1 μg/100 g body weight caused only 40% down-regulation. Down-regulation was also ligand specific. DX was the most effective, whereas even at 100 times the DX dose, corticosterone had only 70% of the effect of DX. DX-induced down-regulation occurred rapidly (within hours), whereas up-regulation in Adx occurred relatively slowly (days), suggesting these two phenomena involve different mechanisms. These results show that the pancreatic glucocorticoid receptor in the suckling rat is under autologous regulation by glucocorticoid. This may constitute an important mechanism in the control of the development of the rat exocrine pancreas.