Differential response of type I and type II corticosteroid receptors to changes in plasma steroid level and circadian rhythmicity

Corticosterone (CORT) binds to two receptor systems in rat brain: the type I CORT-preferring receptor (CR) and the type II glucocorticoid receptor (GR). Discrimination between the two receptor types can be achieved with the 'pure' synthetic glucocorticoid RU 28362. In this study, we show that the binding capacity of GR in the rat hippocampus exhibits a strikingly different response from CR to adrenalectomy (ADX), chronic steroid replacement, hypophysectomy (HYPOX) and during circadian variation. Under those experimental conditions neither receptor site showed changes in binding affinity. After ADX, CR number remained relatively constant for a period of 13 days, while GR capacity increased by 133%, a level which was reached 5 days post-surgery. CR capacity showed circadian variation, since CR number was 65% higher in the evening than in the morning. GR capacities at those two time points were not significantly different. Replacement with subcutaneous CORT implants (100-mg pellets) for 7 days following ADX rats did not affect CR number, but caused a 38% decrease in GR number compared to control animals (cholesterol-treated, 7-day-ADX rats). On the other hand, dexamethasone (DEX) implants (5-, 15-, 25-mg pellets) elicited a dose-dependent increase in CR capacity (up to 99%) and a dose-dependent decrease in GR capacity (40-44%). Finally, 2 weeks after HYPOX, CR and GR numbers were increased by 60 and 38%, respectively. We conclude that the type II GR capacity responds in an autoregulatory manner to changes in circulating plasma glucocorticoid levels, while type I CR does not.