Nuclear receptors outside the nucleus: extranuclear signalling by steroid receptors

Steroid hormone receptors are well known to regulate various aspects of animal physiology by acting as transcriptional regulators in the nucleus. However, it is now evident that these receptors can also be targeted to extranuclear locations (such as the plasma membrane), where they instigate rapid signals that contribute to steroid-mediated cellular responses. Steroid hormone receptors mediate numerous crucial biological processes and are classically thought to function as transcriptional regulators in the nucleus. However, it has been known for more than 50 years that steroids evoke rapid responses in many organs that cannot be explained by gene regulation. Mounting evidence indicates that most steroid receptors in fact exist in extranuclear cellular pools, including at the plasma membrane. This latter pool, when engaged by a steroid ligand, rapidly activates signals that affect various aspects of cellular biology. Research into the mechanisms of signalling instigated by extranuclear steroid receptor pools and how this extranuclear signalling is integrated with responses elicited by nuclear receptor pools provides novel understanding of steroid hormone signalling and its roles in health and disease.