Structure of the GnRH receptor-stimulated signaling network: insights from genomics.

The GnRH receptor influences gene expression in the gonadotrope through activating signaling cascades that modulate transcription factor expression and activity. A longstanding question in neuroendocrinology is how instructions received at the membrane in the form of the pattern of receptor stimulation are processed into specific biosynthetic changes at each gonadotropin promoter. Signal transduction from the membrane to preformed transcription factors relies on recognition of altered conformations. Signal transduction through the layers of the gene network also requires the biosynthesis of new transcription factors. The signal processing of this system depends on its molecular connectivity map and its feedback and feed-forward loops. Review of signal transduction, gene control, and genomic studies provide evidence of key loops that cross between cellular and nuclear compartments. Genomic studies suggest that the signal transduction and gene network form a continuum. We propose that information transfer in the gonadotrope depends on robust signaling modules that serve to integrate events at different time scales across cytoplasmic and nuclear compartments.