ArticlePloS one2009
Negative feedback governs gonadotrope frequency-decoding of gonadotropin releasing hormone pulse-frequency.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Mathematical models in GnRH research.Journal of neuroendocrinology · 2022Review
- Multifaceted Targeting of the Chromatin Mediates Gonadotropin-Releasing Hormone Effects on Gene Expression in the Gonadotrope.Frontiers in endocrinology · 2018Review
- G Protein-Coupled Receptors As Regulators of Localized Translation: The Forgotten Pathway?Frontiers in endocrinology · 2018Review
- Mitogen- and stress-activated protein kinase 1 is required for gonadotropin-releasing hormone-mediated activation of gonadotropin α-subunit expression.The Journal of biological chemistry · 2017Article
- Oscillatory stimuli differentiate adapting circuit topologies.Nature methods · 2017Article
- 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
- Reactive Oxygen Species Link Gonadotropin-Releasing Hormone Receptor Signaling Cascades in the Gonadotrope.Frontiers in endocrinology · 2017Article
- Characterization of Gonadotrope Secretoproteome Identifies Neurosecretory Protein VGF-derived Peptide Suppression of Follicle-stimulating Hormone Gene Expression.The Journal of biological chemistry · 2016Article
- Anti-Müllerian hormone: a new actor of sexual dimorphism in pituitary gonadotrope activity before puberty.Scientific reports · 2016Article
- Article
- Growth differentiation factor 9 (GDF9) forms an incoherent feed-forward loop modulating follicle-stimulating hormone β-subunit (FSHβ) gene expression.The Journal of biological chemistry · 2014Article
- Outside the box signaling: secreted factors modulate GnRH receptor-mediated gonadotropin regulation.Molecular and cellular endocrinology · 2014Review
- Polyribosome and ribonucleoprotein complex redistribution of mRNA induced by GnRH involves both EIF2AK3 and MAPK signaling.Molecular and cellular endocrinology · 2014Article
- Interpreting frequency responses to dose-conserved pulsatile input signals in simple cell signaling motifs.PloS one · 2014Article
- Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network.Frontiers in endocrinology · 2013Review
- GnRH-Induced Ca(2+) Signaling Patterns and Gonadotropin Secretion in Pituitary Gonadotrophs. Functional Adaptations to Both Ordinary and Extraordinary Physiological Demands.Frontiers in endocrinology · 2013Review
- Decoding GnRH neurohormone pulse frequency by convergent signalling modules.Journal of the Royal Society, Interface · 2012Article
- Pharmacological chaperones for misfolded gonadotropin-releasing hormone receptors.Advances in pharmacology (San Diego, Calif.) · 2011Review
- Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The synthesis of the gonadotropin subunits is directed by pulsatile gonadotropin-releasing hormone (GnRH) from the hypothalamus, with the frequency of GnRH pulses governing the differential expression of the common alpha-subunit, luteinizing hormone beta-subunit (LHbeta) and follicle-stimulating hormone beta-subunit (FSHbeta). Three mitogen-activated protein kinases, (MAPKs), ERK1/2, JNK and p38, contribute uniquely and combinatorially to the expression of each of these subunit genes. In this study, using both experimental and computational methods, we found that dual specificity phosphatase regulation of the activity of the three MAPKs through negative feedback is required, and forms the basis for decoding the frequency of pulsatile GnRH. A fourth MAPK, ERK5, was shown also to be activated by GnRH. ERK5 was found to stimulate FSHbeta promoter activity and to increase FSHbeta mRNA levels, as well as enhancing its preference for low GnRH pulse frequencies. The latter is achieved through boosting the ultrasensitive behavior of FSHbeta gene expression by increasing the number of MAPK dependencies, and through modulating the feedforward effects of JNK activation on the GnRH receptor (GnRH-R). Our findings contribute to understanding the role of changing GnRH pulse-frequency in controlling transcription of the pituitary gonadotropins, which comprises a crucial aspect in regulating reproduction. Pulsatile stimuli and oscillating signals are integral to many biological processes, and elucidation of the mechanisms through which the pulsatility is decoded explains how the same stimulant can lead to various outcomes in a single cell.
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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.