Changes in plasma adrenocorticotropin, corticosterone, corticosteroid-binding globulin, and hippocampal glucocorticoid receptor occupancy/translocation in rat pups in response to stress.

Abstract

Pituitary-adrenal responses to stress in the neonatal rat have been reported to be substantially reduced compared to older animals (i.e. a stress hyporesponsive period). This supposed period of endocrine quiescence is characterized by reduced stress-induced increases in both plasma ACTH and corticosterone. At the same time a number of authors have noted the decreased plasma corticosteroid-binding globulin (CBG) levels of the neonate, and there is evidence for an increased percentage of free corticosterone as well as age-related changes in the volume of distribution for corticosterone. These findings suggest that the reduced CBG levels might enhance the biological significance of existing glucocorticoid levels, beyond that assumed on the basis of plasma total corticosterone levels. We examined this question by estimating hippocampal glucocorticoid receptor occupancy and 'translocation' in Day 6, Day 15, and adult animals under basal and stressful conditions. The results showed that: 1) plasma ACTH levels were elevated in Day 6 animals in response to acute exposure to ether, maternal separation, and maternal separation + ether, however, ACTH responses were substantially lower than in Day 15 or adult animals; 2) Plasma total corticosterone levels followed a similar pattern; most noteworthy was the potent glucocorticoid response in Day 15 animals to the combination of maternal separation + ether; 3) Plasma CBG levels in Day 6 animals were extremely low (< 3% adult values); by Day 15 CBG levels were about 25% of adult levels. Interestingly, maternal separation was associated with a substantial decrease in plasma CBG levels; 4) Hippocampal glucocorticoid receptor occupancy/translocation was similar at all ages under both basal and stress conditions. The only notable exception occurred during maternal separation in Day 15 animals, where the percentage of hippocampal glucocorticoid receptor occupancy/translocation was higher than that observed at any time in either Day 6 or adult animals. This finding is likely related to the decrease in plasma CBG that occurs following separation of Day 15 pups from the dam. Thus, despite the higher corticosterone level in the adult, the increase in glucocorticoid receptor occupancy/translocation was generally comparable across all ages either under basal conditions, or following stress. These receptor data underscore the importance of developmental changes in plasma CBG levels.