ArticleThe Journal of biological chemistry2009
Pulsatile and sustained gonadotropin-releasing hormone (GnRH) receptor signaling: does the Ca2+/NFAT signaling pathway decode GnRH pulse frequency?
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 56 citations in OpenAlex.
- Emerging human cell-based in vitro models for studying pituitary development and disorders.Endocrine journal · 2026Review
- The E3 ubiquitin ligase RNF216/TRIAD3 is a key coordinator of the hypothalamic-pituitary-gonadal axis.iScience · 2022Article
- Mathematical models in GnRH research.Journal of neuroendocrinology · 2022Review
- A role for NPY-NPY2R signaling in albuminuric kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- SRXN1 Is Necessary for Resolution of GnRH-Induced Oxidative Stress and Induction of Gonadotropin Gene Expression.Endocrinology · 2019Article
- Regulation and Function of C-Type Natriuretic Peptide (CNP) in Gonadotrope-Derived Cell Lines.Cells · 2019Article
- GnRH-A Key Regulator of FSH.Endocrinology · 2019Review
- Regulation of reproduction via tight control of gonadotropin hormone levels.Molecular and cellular endocrinology · 2018Review
- Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression.Molecular and cellular endocrinology · 2018Review
- Mathematical modeling of gonadotropin-releasing hormone signaling.Molecular and cellular endocrinology · 2017Review
- Modeling and high-throughput experimental data uncover the mechanisms underlyingThe Journal of biological chemistry · 2017Article
- Information Transfer via Gonadotropin-Releasing Hormone Receptors to ERK and NFAT: Sensing GnRH and Sensing Dynamics.Journal of the Endocrine Society · 2017Article
- Information Transfer in Gonadotropin-releasing Hormone (GnRH) Signaling: EXTRACELLULAR SIGNAL-REGULATED KINASE (ERK)-MEDIATED FEEDBACK LOOPS CONTROL HORMONE SENSING.The Journal of biological chemistry · 2016Article
- Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation.Integrative biology : quantitative biosciences from nano to macro · 2015Article
- GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression.Molecular and cellular endocrinology · 2014Review
- Pulsatile hormonal signaling to extracellular signal-regulated kinase: exploring system sensitivity to gonadotropin-releasing hormone pulse frequency and width.The Journal of biological chemistry · 2014Article
- Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK signaling.Molecular and cellular endocrinology · 2014Article
- Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network.Frontiers in endocrinology · 2013Review
- GnRH pulse frequency-dependent stimulation of FSHβ transcription is mediated via activation of PKA and CREB.Molecular endocrinology (Baltimore, Md.) · 2013Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Gonadotropin-releasing hormone (GnRH) acts via 7 transmembrane region receptors on gonadotrophs to stimulate synthesis and secretion of the luteinizing hormone and follicle-stimulating hormone. It is secreted in pulses, and its effects depend on pulse frequency, but decoding mechanisms are unknown. Here we have used (nuclear factor of activated T-cells 2 (NFAT2)-emerald fluorescent protein) to monitor GnRH signaling. Increasing [Ca(2+)](i) causes calmodulin/calcineurin-dependent nuclear NFAT translocation, a response involving proteins (calmodulins and NFATs) that decode frequency in other systems. Using live cell imaging, pulsatile GnRH caused dose- and frequency-dependent increases in nuclear NFAT2-emerald fluorescent protein, and at low frequency, translocation simply tracked GnRH exposure (albeit with slower kinetics). At high frequency (30-min intervals), failure to return to basal conditions before repeat stimulation caused integrative tracking, illustrating how the relative dynamics of up- and downstream signals can increase efficiency of GnRH action. Mathematical modeling predicted desensitization of GnRH effects on [Ca(2+)](i) and that desensitization would increase with dose, frequency, and receptor number, but no such desensitization was seen in HeLa and/or LbetaT2 cells possibly because pulsatile GnRH did not reduce receptor expression (measured by immunofluorescence). GnRH also caused dose- and frequency-dependent activation of alphaGSU, luteinizing hormone beta, and follicle-stimulating hormone beta luciferase reporters, effects that were blocked by calcineurin inhibition. Pulsatile GnRH also activated an NFAT-responsive luciferase reporter, but this response was directly related to cumulative pulse duration. This together with the lack of desensitization of translocation responses suggests that NFAT may mediate GnRH action but is not a genuine decoder of GnRH pulse frequency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.