New evidence for estrogen receptors in gonadotropin-releasing hormone neurons

Estrogen exerts a critical regulatory influence upon the biosynthetic and secretory activity of the gonadotropin-releasing hormone (GnRH) neurons. It seems likely that estrogen regulates the behavior of the GnRH neuron through multiple transsynaptic, neuronal-glial, and direct membrane modes of action. Advances in our understanding of these mechanisms over the last 3 years are highlighted. In addition, very recent studies have begun to provide evidence for the expression of estrogen receptors (ERs) in GnRH neurons in the rodent. Although not yet firmly established, the current consensus supports the hypothesis that GnRH neurons express ERbeta. Evidence exists for ERbeta mRNA expression by GnRH neurons throughout development and ERbeta immunoreactivity has now also been detected in these cells. Murine GnRH neurons have further been shown to express estrogen receptor-related receptor-alpha, an orphan receptor thought to constitutively activate estrogen response elements. Together, these findings provide a cornerstone for the reassessment of the role of ERs and related receptors in the direct genomic and potential nontranscriptional actions of estrogen upon the GnRH neuron.