GnRH (gonadotropin-releasing hormone) mediates control of reproduction. It is secreted in pulses and acts via intracellular effectors to activate gene expression. Submaximal GnRH pulse frequency can elicit maximal responses, yielding bell-shaped frequency–response curves characteristic of genuine frequency decoders. GnRH frequency decoding is therapeutically important (pulsatile GnRH can drive ovulation in assisted reproduction, whereas sustained activation can treat breast and prostate cancers), but the mechanisms are unknown. In the present paper, we review recent work in this area, placing emphasis on the regulation of transcription, and showing how mathematical modelling of GnRH effects on two effectors [ERK (extracellular-signal-regulated kinase) and NFAT (nuclear factor of activated T-cells)] reveals the potential for genuine frequency decoding as an emergent feature of the GnRH signalling network, rather than an intrinsic feature of a given protein or pathway within it.
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February 2012
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Conference Article|
January 19 2012
Decoding neurohormone pulse frequency by convergent signalling modules
Krasimira Tsaneva-Atanasova;
Krasimira Tsaneva-Atanasova
*Bristol Centre for Applied Nonlinear Mathematics, Department of Engineering Mathematics, University of Bristol, Bristol BS8 1TR, U.K.
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Christopher J. Caunt;
Christopher J. Caunt
†Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, U.K.
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Stephen P. Armstrong;
Stephen P. Armstrong
‡Steroid Hormones Section, Clinical Endocrinology Branch, NIDDK, National Institutes of Health, Bethesda, MD 20892, U.S.A.
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Rebecca M. Perrett;
Rebecca M. Perrett
§Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Science, University of Bristol, Whitson Street, Bristol BS1 3NY, U.K.
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Craig A. McArdle
Craig A. McArdle
1
§Laboratories for Integrative Neuroscience and Endocrinology, School of Clinical Science, University of Bristol, Whitson Street, Bristol BS1 3NY, U.K.
1To whom correspondence should be addressed (email craig.mcardle@bristol.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 30 2011
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem Soc Trans (2012) 40 (1): 273–278.
Article history
Received:
June 30 2011
Citation
Krasimira Tsaneva-Atanasova, Christopher J. Caunt, Stephen P. Armstrong, Rebecca M. Perrett, Craig A. McArdle; Decoding neurohormone pulse frequency by convergent signalling modules. Biochem Soc Trans 1 February 2012; 40 (1): 273–278. doi: https://doi.org/10.1042/BST20110645
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