Endocrine Abstracts

As we learn more and more about the complexity of biological systems there is a real risk of being drowned in data but starved of information. This is increasingly recognised by grant funders and is certainly true of the signal transduction field where the complexity of signaling networks makes our traditional intuitive approaches look increasingly inadequate. For my own work on GnRH signaling, one solution has been to collaborate with mathematicians and engineers. Success in ...

Gonadotropin-releasing hormone (GnRH) is a hypothalamic neuropeptide that acts via GnRHR on the pituitary gonadotrope. It is secreted in pulses and acts via GnRHR to activate ERK and Nuclear Factor of Activated T-cells (NFAT), mediating GnRH effects on gonadotropin expression. We monitor their activation by high content imaging (fluorescence staining for ppERK and nuclear translocation of an NFAT1c-EFP reporter) in fixed LbT2 gonadotroph cells. Single cell measures reveal high...

GnRH is secreted in pulses and its effects on pituitary gonadotropes depend on pulse frequency. This is crucial for physiological control and therapeutic manipulation of the system (in IVF and treatment of hormone-dependent cancers) but GnRH pulse frequency decoding mechanisms are unknown. The simplest form of frequency dependence is a linear relationship between integrated inputs and outputs but such ‘integrative tracking’ cannot explain the bell-shaped frequency-re...

GnRH acts via G-protein coupled receptors to stimulate phospholipase C. This activates protein kinases C, driving the activation of extracellular signal regulated kinases (ERKs) that mediates transcriptional effects of GnRH. GnRH is secreted in pulses that cause rapid, transient and reproducible ERK activation (1). ERK response kinetics dictate biological consequences in many systems and, although GnRH-mediated ERK activation has been thoroughly explored, little is known about...

GnRH acts via G-protein coupled receptors to stimulate synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. GnRH activates phospholipase C, causing calcium mobilisation and influx, activation of protein kinase C and stimulation of mitogen-activated protein kinase cascades. GnRH is secreted in brief pulses with each pulse causing rapid and transient activation of extracellular signal regulated kinases (ERKs) (1), yet very little is known about what s...

Epidermal growth factor (EGF) and heregulin (HRG) act via ErbB receptors, to stimulate Akt and ERK. These drive breast cancer cell proliferation and the network is targeted in cancer therapy (1). Single cell responses show marked cell-cell variation and information theory provides statistical measures that take the effect this noise has on information transfer into account (2). Here we quantify the mutual information (MI) between stimulus concentration and effects in MCF7 cell...

Glomerular podocytes are directly regulated by insulin (1) and podocyte insulin resistance is implicated in diabetic kidney disease. Information theory derived statistical measures can be used to quantify information transfer via cell signalling pathways (2). This novel approach takes into account cell-cell variation in responses and the impact that this noise has on information transfer but has not yet been applied to signalling in podocytes. Here we quantify the mutual infor...

Highly regulated pulsatile secretion of the GnRH is essential for reproduction. GnRH pulses act via 7TM receptors to control synthesis and secretion of FSH and LH. GnRH receptors activate a signal-transduction network that includes two parallel pathways mediated by ERK and nuclear factor of activated T cells (NFAT). ERK and NFAT in concert with other effectors mediate transcriptional regulation of FSHβ and LHβ genes following stimulation by pulsatil...

Single cell measurements of signalling proteins typically reveal high cell–cell variability raising questions about how reliably individual cells sense their environment in order to make decisions. Information theoretic approaches can be used to explore such sensing, treating cell signalling pathways as ‘noisy’ communication channels. Mutual information (MI) can be calculated between system inputs and outputs as a statistical measure of the reliability of sensin...

One way in which cells receive information about their environment is through hormones binding to appropriate receptors on their cell surface. Single cell measurements of signalling proteins typically reveal high cell–cell variability raising questions about how reliably individual cells sense their environment in order to make decisions. Information theoretic approaches can be used to explore such sensing, treating cell signalling pathways as ‘noisy’ communicat...