Nuclear receptor coactivators in neuroendocrine function

Abstract

Steroid hormones influence a variety of neuroendocrine events, including brain development, sexual differentiation and reproduction. Hormones elicit many of these effects by binding to neuronal steroid receptors, which are members of a nuclear receptor superfamily of transcriptional activators. However, the mechanisms by which activated steroid receptors regulate gene expression in brain are not well understood. Recently, a new class of proteins, known as nuclear receptor coactivators, have been found to dramatically enhance steroid receptor mediated transactivation of genes in vitro. Here, the proposed molecular mechanisms of how these coactivators enhance the transcriptional activity of steroid receptors are summarized. While much is known about the mechanisms of these coactivators in vitro, it is unclear how these cofactors function in hormone action in vivo or in the brain. This paper discusses some of the initial and enticing investigations into the role of these important coregulatory proteins in neuroendocrine events. Finally, some of the critical issues and future directions in nuclear receptor coactivator function in neuroendocrinology are highlighted.