The development of the glucocorticoid receptor system in the rat limbic brain. III. Negative-feedback regulation

In the neonatal rat, there are parallel increases with age in the concentrations of glucocorticoid receptors in the limbic system, and in the sensitivity of the hypothalamic-pituitary-adrenal (HPA) axis to negative-feedback inhibition by circulating glucocorticoids. We speculated that the increasing receptor concentrations may mediate this increasing sensitivity of the HPA axis to the suppressive effects of glucocorticoids. To examine this idea we treated rats with exogenous corticosterone from days 29 to 34, resulting in a down-regulation of glucocorticoid receptors in the brain at Day 35 to levels similar to those of younger animals. Subjects whose maturational increase in receptors was reversed in this manner were less sensitive to feedback inhibition of glucocorticoids. Specifically, compared to controls they continued to secrete corticosterone after the end of stress, and were relatively insensitive to the suppressive effects of the synthetic glucocorticoid, dexamethasone, on corticosterone titers. Our data specifically implicate the hippocampus in modulating feedback sensitivity, as down-regulation was extensive in this structure, and did not occur in the septum, amygdala, hypothalamus or pituitary.