OBJECTIVES: The regulation of splicing by glucocorticoids in the hippocampus has not been well studied. Hence, this study aims to determine the transcripts/exons that are regulated by stress hormones in the hippocampus. RESULTS: Hypophysectomy was confirmed by weight reduction in experimental animals. Serum corticosterone was also reduced upon hypophysectomy which was rescued by administration of CORT or ACTH. Using RNA-Seq, we identified transcripts/exons that are changed upon hypophysectomy and successfully rescued by CORT or ACTH. Specifically, edgeR and DEXSeq identified 32 genes with >2 fold changes and 889 exons with >1.5 fold changes respectively that were changed upon hypophysectomy and rescued by CORT or ACTH administration. RT-PCR validated the regulation of several target exons by stress hormones. We further identified a decline and an increase in the transcripts containing the target exon of the Sept8 gene in a time-course dependent manner upon hypophysectomy and in normal groups respectively. CONCLUSION: These findings demonstrate a specific exon that is regulated by stress hormones in the hippocampus.