title: Decoding neurohormone pulse frequency by convergent signalling modules.
abstract: 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.
authors.affiliation: Bristol Centre for Applied Nonlinear Mathematics, Department of Engineering Mathematics, University of Bristol, Bristol BS8 1TR, UK.
authors.forename: Krasimira
authors.initials: K
authors.lastname: Tsaneva-Atanasova
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Caunt
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Armstrong
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Perrett
authors.forename: Craig A
authors.initials: CA
authors.lastname: McArdle
mesh_terms: D000465:Algorithms; D000818:Animals; D020013:Calcium Signaling; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D050778:NFATC Transcription Factors / Q000378:metabolism; D021381:Protein Transport
chemical_list: D050778:NFATC Transcription Factors; D007987:Gonadotropin-Releasing Hormone; D048049:Extracellular Signal-Regulated MAP Kinases