Endocrine Abstracts

GnRH acts via Gq/11-coupled GPCRs on gonadotropes to control synthesis and secretion of LH and FSH. We use mathematical and statistical approaches as well as automated cell imaging to explore this system. In cells expressing ERK2–GFP and GnRH receptors, GnRH pulses cause rapid and transient nuclear translocation of ERK2–GFP, providing a live-cell readout for ERK activation¹. A mathematical model trained against this data predicted greater sensitivity to receptor number than to GnRH concentration. It also predicted greater sensitivity to pulse frequency than to pulse width because of activation continuing beyond the GnRH pulse. Each of these predictions was confirmed experimentally. Single-cell ERK measures can also be used to quantify the efficiency of information transfer. Specifically, mutual information (MI) measures accuracy of information processing, as the maximal number of inputs a cell can resolve without error². To measure MI we expressed Egr1-zsGREEN (an imaging readout for ERK-driven transcription) in LβT2 cells and also stained for ppERK1/2, constructing concentration–response curves at varied times. Imaging data from ~100 000 individual cells and imposing a uniform input distribution over the GnRH concentration range revealed ppERK1/2 MI values increasing rapidly to ~0.8 bits at 5 min, then reducing to ~0.6 bits at 240 min. MI for Egr1-zsGREEN increased from <0.1 to ~ 0.8 bits between 60 and 240 min, revealing the time-dependent transfer of information from ERK1/2 to the transcriptional readout. MI of 1 bit has been interpreted as meaning that individual cells can distinguish only two states of the environment². Our data therefore indicate inefficient information processing, in spite of the fact that GnRH effects are graded over a broad concentration range. This could reflect the importance of additional information from other branches of the signalling network.

References: 1. Armstrong SP et al. J Biol Chem 2010 285 24360.

2. Cheong R et al. Science 2011 334 354.