Glucocorticoid receptors in brain and pituitary of the lactating rat

The female rat exhibits elevated corticosterone levels throughout lactation, suggesting a possible dampening of the sensitivity of adrenocortical negative-feedback processes during this period. Negative-feedback within the adrenocortical axis is, in large part, mediated by an enhanced hormone receptor signal at a number of glucocorticoid target sites, including the pituitary, hypothalamus, and hippocampus. In the study reported here we have measured glucocorticoid receptor binding capacity in soluble fractions prepared from these tissues, using an in vitro binding assay with [3H]dexamethasone as radioligand. We found that during at least the first two weeks of lactation the rat shows significantly decreased [3H]dexamethasone binding capacity in the hippocampus, with no change in pituitary or the hypothalamus during lactation. These data provide one possible mechanism whereby a critical target region for adrenocortical negative-feedback might be desensitized to circulating glucocorticoids, thus permitting the sustained elevation in pituitary-adrenal activity.