Minireview: Neuronal Steroid Hormone Receptors: They’re Not Just for Hormones Anymore

The ovarian steroid hormones have numerous effects on the brain, many of which are mediated, at least in part, by interaction with intracellular steroid hormone receptors acting as regulators of transcription. These intracellular steroid hormone receptors have often been considered to be activated solely by cognate hormone. However, during the past decade, numerous studies have shown that the receptors can be activated by neurotransmitters and intracellular signaling systems, through a process that does not require hormone. Although most of these have been in vitro experiments, others have been in vivo. Evidence from a wide variety of tissues and cells suggests that steroid hormone receptors are transcription factors that can be activated by a wide variety of factors, only one of which is cognate hormone. Furthermore, ligand-independent activation of neural steroid hormone receptors, rather than being a pharmacological or in vitro curiosity, seems to be a process that occurs in the normal physiology of animals. Thinking of steroid hormone receptors only as ligand-activated proteins may constrain our thinking about the many factors that may activate the receptors and cause receptor-dependent changes in neural gene expression and neuroendocrine function.