Fetal exposure to excess glucocorticoids (GC) programs the developing hypothalamo-pituitary-adrenal (HPA) axis, and may predispose offspring to adult-onset disease. During development, serotonin (5-HT) influences transcription of hippocampal GR mRNA via the 5-HT7 receptor. The effect of 5-HT on GR involves the transcription factor NGFI-A. Given the developmental changes which we have previously reported in hippocampal GR mRNA expression, we hypothesized that; 1) there are progressive developmental changes in 5-HT7 receptor and NGFI-A mRNA expression in the fetal guinea pig limbic system, and 2) that repeated exposure to synthetic GC treatment will significantly modify developmental expression of these genes. 5-HT7 receptor mRNA was highly expressed in the hippocampus and thalamus at gd40 (term~70 days), and significantly decreased (p<0.05) with advancing gestation. Conversely, NGFI-A mRNA expression in the hippocampus and frontal cortex was almost undetectable at gd40, but was dramatically elevated (p<0.05; 8-fold) near term. Changes in mRNA were refelected by NGFI-A protein levels. These changes were significantly correlated to hippocampal GR expression and fetal plasma cortisol concentrations. Synthetic GC treatment increased NGFI-A mRNA levels in CA1 and the cingulate cortex, but had no effect on 5-HT7 receptor expression. In conclusion our results suggest: 1) that limbic 5-HT7 receptor expression is not directly linked to maturation of hippocampal GR in late gestation. 2) The upregulation of NGFI-A expression near term is driven by glucocorticoid and, 3) that premature exposure to synthetic glucocorticoid significantly increases transcriptional activity in the fetal limbic system.