Modulation of hormonal signaling in the brain by steroid receptor coactivators

Nuclear receptors, such as estrogen, glucocorticoid or thyroid hormone receptors, have been shown to play a critical role in brain development and physiology. The activity of these receptors is modulated by the interaction with several proteins and, in particular, coactivators are required to enhance their transcriptional activity. The steroid receptor coactivators (SRC-1, -2 and -3) are currently the best characterized coactivators and we review here the current knowledge on the distribution and function of these proteins in the brain. Knock-out models and antisense techniques have demonstrated the requirement for SRC-1 and -2 in the brain, focusing mainly on steroid and thyroid hormone-dependent development and behavior. The precise function of SRC-3 in the brain is currently unknown but its presence throughout the brain suggests an important function. Although the molecular biology of SRCs is relatively well known, the in vivo control of their expression, post-translational modifications and time- and cell-specific interactions with the different nuclear receptors remain elusive. A complete understanding of hormone action on brain and behavior will not be attained until a better knowledge of coactivator physiology is achieved.