Synergistic gene regulation by thyroid hormone and glucocorticoid in the hippocampus

The hippocampus is considered the center for learning and memory in the brain, and its development and function is greatly affected by the thyroid and stress axes. Thyroid hormone (TH) and glucocorticoids (GC) are known to have a synergistic effect on developmental programs across several vertebrate species, and their effects on hippocampal structure and function are well-documented. However, there are few studies that focus on the processes and genes that are cooperatively regulated by the two hormone axes. Cross-regulation of the thyroid and stress axes in the hippocampus occurs on multiple levels such that TH can regulate the expression of the GC receptor (GR) while GC can modulate tissue sensitivity to TH by controlling the expression of TH receptor (TR) and enzymes involved in TH biosynthesis. Thyroid hormone and GC are also known to synergistically regulate the transcription of genes associated with neuronal function and development. Synergistic gene regulation by TH and GC may occur through the direct, cooperative action of TR and GR on common target genes, or by indirect mechanisms involving gene regulatory cascades activated by TR and GR. In this chapter, we describe the known physiological effects and underlying molecular mechanisms of TH and GC synergistic gene regulation in the hippocampus.