The proto-oncogenes, cfos/cjun, are co-localized with thyrotropin-releasing hormone (TRH) in cultured anterior pituitary cells and increase following exposure to dexamethasone (Dex). To assess the role of cfos and cjun in the Dex stimulation of TRH gene expression, we used antisense oligonucleotides to block cfos and cjun expression in order to reduce formation of activating protein-1 (AP-1). The results showed that the antisense oligonucleotides together effectively reduced cfos/cjun gene expression and consequently the glucocorticoid stimulation of TRH peptide and mRNA. The findings indicate that cfos/cjun are involved in the glucocorticoid activation of TRH gene expression.