Diversity of ovarian steroid signaling in the hypothalamus

It is well known that many of the actions of gonadal steroids in hypothalamic neurons are mediated via intracellular receptor/transcription factors that interact with steroid response elements on target genes. Since the cloning of the intracellular steroid receptors/transcription factors, it has been assumed that most if not all of the actions of the gonadal steroids are mediated via these intracellular receptors. However, there now exist compelling evidence for membrane (G-protein-coupled) steroid receptors for estrogen and progesterone in hypothalamic and other brain neurons. But, it is not well understood how steroids signal via membrane receptors, and how these signals impact not only membrane excitability but also gene transcription in hypothalamic neurons. Indeed, it has been known for sometime that gonadal steroids can rapidly alter hypothalamic neuronal activity within seconds, indicating that some cellular effects can occur via membrane delimited events. In addition, gonadal steroids can affect second messenger systems, including calcium and various kinases to prompt and/or alter cell signaling. Therefore, this chapter will consider our current knowledge of rapid (i.e., seconds to minutes) membrane-initiated and intracellular signaling as well as classical nuclear receptor signaling by gonadal steroids in hypothalamic neurons, the nature of these receptors and how they contribute to homeostatic functions.