Ontogeny of hippocampal corticosteroid receptors: Effects of antenatal glucocorticoids in human and mouse

Abstract

Women at risk for preterm delivery are treated with synthetic glucocorticoids (GCs) to enhance fetal lung maturation. GCs can bind to two intracellular receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), which function as transcription factors. Both are highly expressed in the hippocampus. Several studies have focused on adverse side effects of antenatal GC treatment. However, relatively little is known about the ontogeny of GR and MR, especially in human. Therefore, we studied the ontogeny of both receptors in the human and mouse hippocampus and investigated the effects of antenatal dexamethasone (dex) treatment, a synthetic glucocorticoid, on MR and GR mRNA levels during hippocampal development. The results demonstrate that MR mRNA was first expressed in mouse hippocampus at embryonic day (E)15.5, at the timepoint when dex was administered. In contrast, GR mRNA expression was first observed after birth at postnatal day (P)5. However, in the human hippocampus both receptors are expressed at 24 weeks of gestation, when antenatal GCs are administered in clinical practice. Quantitative in situ hybridization demonstrated that MR mRNA levels were reduced only shortly after dex treatment at E16, but were unaffected from E18 onwards. These findings indicate that a single antenatal dex administration at E15.5 transiently affects MR mRNA levels in the mouse hippocampus. No effect of antenatal dex treatment was found on the human hippocampus at the third trimester of pregnancy. These data on the prenatal ontogeny of both corticosteroid receptors in the human hippocampus is important for understanding the significance of fetal glucocorticoid or stress exposure and its potential effects on health and disease.