Prenatal stress and glucocorticoid effects on the developing gender-related brainProceedings of Xth International Congress on Hormonal Steroids, Quebec, Canada, 17–21 June 1998.

Abstract

Hormonal and neurotransmitter environment of nondifferentiated cells in the developing brain determines many of gender-specific behavioural and neuroendocrine functions. Early postnatal and long-term effects of maternal stress or prenatal glucocorticoid on sex-related peculiarities of the brain morphology, biogenic monoamine turnover, testosterone metabolism, hypothalamic noradrenaline (NA) and adrenocortical responses to an acute stress were studied in Wistar rat offsprings. Maternal stress (1 h immobilization daily for gestational days 15–21) prevented development of sexual dimorphism in neuronal cell nuclei volumes in suprachiazmatic nucleus (SCN) in 10 day old pups. That was associated with a disappearance of male–female differences in NA and 5-hydroxytryptamine turnover in the preoptic area (POA) and dopamine (DA) turnover in the mediobasal hypothalamus (MBH) by decreasing them in male pups. Hydrocortisone acetate (5 mg daily during the last week of pregnancy) produced changes in NA turnover in the POA of males and females which were quite similar to those after maternal stress. Changes in aromatase and 5α-reductase activities in the POA of male pups were quite opposite as affected by maternal stress or prenatal glucocorticoid. Sexual differences in 5α-reductase activity in the MBH appeared due to its increase in prenatally stressed male pups. In contrast to adult males, in adult females maternal stress did not restrict hypothalamic NA and blood plasma corticosterone response to acute stress (1 h immobilization). Our findings on morphology and functions of gender-related developing brain areas stand in correlation with modifying effects of maternal stress and prenatal glucocorticoid on behavior and neuroendocrine regulations.

Introduction

Organizing effects of gonadal and adrenocortical steroids on mammalian developing brain is a matter of fact that is generally recognized by neurobiologists. Despite the fact that brain development and its plasticity (neuronal growth, synaptogenesis, cellular communications) depend mainly on genetic program and intrinsic signals, many perinatal agents like stress, natural and synthetic glucocorticoids, neuropeptides, gonadal steroids are capable of modifying the brain morphology, chemistry and physiology. They exert the imprinting effects on steroid receptors, neurotransmitter synthesis, metabolism and receptors, expression of specific proteins, etc.

In 1972 I. Ward published a milestone work on feminizing effect of maternal stress on sexual behavior in adult male rat offspring[1]. Then G. Dörner reported about the disruption of brain sexual differentiation (BSD) in men as a result of maternal or the so-called prenatal stress (PS)[2]. Now new evidences demonstrating that early exposure of pregnant mammals to stress, hormone and neurotransmitter imbalance generates irreversible long-term alterations of behavior, neuroendocrine control of reproduction and stress-responsiveness of the hypothalamus–pituitary–adrenocortical (HPA) axis in the offspring have appeared3, 4, 5, 6. These phenomena are suggested to occur due to stress-induced changes of catecholamine (CA) and sex steroids contents in dams and fetuses. Maternal stress lowers CA concentration and steroid aromatase activity (AA) in the brain and decreases blood plasma testosterone (T) and luteinizing hormone levels in fetuses and newborn male rats7, 8, 9, 10, 11. T or tyrosine, CA precursor, administration to pregnant rats prevents long-term disturbances of sexual behavior in adulthood induced by PS12, 13.

Long-term effects of maternal stress on stress-induced HPA reactivity and sexual behavior in adult male rat offspring may be caused by endogenous hypercorticoidism1, 4, 14. In this connection neuroendocrine effects of prenatally administered glucocorticoid are of particular interest because of an increase of adrenocortical steroids in maternal blood and their ability to cross placental and blood–brain barriers. Nevertheless, mechanisms underlying perinatal stress and hormonal modification of neuroendocrine system are not well understood yet.

This paper reviews our recent results on prenatal stress or glucocorticoid effects on gender-related developing brain and HPA stress-responsiveness.