Prenatal stress: consequences of glucocorticoids on hippocampal development and function.

Prenatally stressed offspring exhibit a variety of physiological and behavioral alterations. This paper highlights those alterations associated with prenatal stress-induced elevations in glucocorticoid secretion. Three major alterations are identified that may be produced by glucocorticoid-induced actions on the developing hippocampus. Changes include reductions in steroid receptors that bind endogenous glucocorticoids, enhanced secretion of stress hormones and increased reactivity or emotionality in stressful situations. Some of these alterations may be ameliorated by early postnatal environmental manipulations such as adoption and handling procedures. These latter results suggest that prenatal stress-induced effects of glucocorticoids extend into the early postnatal period to produce long-term hippocampal and behavioral alterations. Support for this hypothesis is based on studies demonstrating that the hippocampus undergoes considerable maturational changes during the early postnatal period such as establishing the regional distribution of corticosteroid receptor densities and development of hippocampal dentate gyrus cells as well as cholinergic systems. Hippocampal corticosteroid receptors are involved in the regulation of glucocorticoid negative feedback and hippocampal dentate gyrus and cholinergic development are influenced by endogenous glucocorticoids and are implicated in the development of defensive or stress-induced behavior. The developing hippocampus appears especially vulnerable to alterations induced by prenatal stress-induced elevations in glucocorticoids that continue to produce their effects throughout the early postnatal period.