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Mathematical and biochemical 'design features' for cell decoding of pulses revealed
Date:3/13/2014

Every cell in the body has to sense and respond to chemicals such as hormones and neurotransmitters. They do so by relaying information from receptors to intracellular biochemical pathways that control cell behaviour, but relatively little is known about how cells decode the information in dynamic stimuli.

A team of researchers have found that differences in response kinetics working down the intracellular signalling pathway dictate differential sensitivity to different features of pulsatile hormone inputs.

The study funded by the BBSRC and published today [14 March] in the Journal of Biological Chemistry, explored mechanism underlying dynamic gonadotropin-releasing hormone (GnRH) signalling using live cell imaging and mathematical modelling.

The research team, led by Craig McArdle, Professor of Molecular Pharmacology at the University of Bristol's School of Clinical Sciences, in collaboration with the University of Exeter, focused on the ERK signalling pathway as this enzyme is activated by GnRH pulses and is essential for normal reproduction.

The neuropeptide hormone GnRH is secreted in pulses from neurons in the hypothalamus and controls secretion of two pituitary hormones, the LH and FSH that, in turn, control production of germ cells and sex steroids.

This system provides the interface between the brain and the reproductive system. It is absolutely essential for normal reproduction and is targeted therapeutically in assisted reproduction and in the treatment of hormone-dependent diseases, such as breast and prostate cancer.

The study found that for effects on gene expression the system is more sensitive to changes in GnRH receptor number than it is to changes in GnRH concentration, and is more sensitive to changes in GnRH interval than it is to changes in GnRH pulse width.

Professor Craig McArdle said: "The work revealed "design-features" of the system that make perfect sense in ligh
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Contact: Joanne Fryer
press-office@bristol.ac.uk
44-117-331-7276
University of Bristol
Source:Eurekalert

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