ArticleProceedings of the National Academy of Sciences of the United States of America2003
An agonist-induced switch in G protein coupling of the gonadotropin-releasing hormone receptor regulates pulsatile neuropeptide secretion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 142 citations in OpenAlex.
- Hypothalamus Transcriptome Reveals Key lncRNAs and mRNAs Associated with Fecundity in Goats.Animals : an open access journal from MDPI · 2025Article
- History of the Development of Knowledge about the Neuroendocrine Control of Ovulation-Recent Knowledge on the Molecular Background.International journal of molecular sciences · 2024Review
- GnRH-driven FTO-mediated RNA mBMC biology · 2024Article
- Modelling KNDy neurons and gonadotropin-releasing hormone pulse generation.Current opinion in endocrine and metabolic research · 2022Review
- Chromosome-Level Assembly of MaleBiology · 2022Article
- Mathematical models in GnRH research.Journal of neuroendocrinology · 2022Review
- Anti-metastatic effect of GV1001 on prostate cancer cells; roles of GnRHR-mediated Gαs-cAMP pathway and AR-YAP1 axis.Cell & bioscience · 2021Article
- GnRH-A Key Regulator of FSH.Endocrinology · 2019Review
- Gonadotropin regulation by pulsatile GnRH: Signaling and gene expression.Molecular and cellular endocrinology · 2018Review
- The Arg-Phe-amide peptide 26RFa/glutamine RF-amide peptide and its receptor: IUPHAR Review 24.British journal of pharmacology · 2017Review
- The potential regulatory mechanisms of the gonadotropin-releasing hormone in gonadotropin transcriptions identified with bioinformatics analyses.Reproductive biology and endocrinology : RB&E · 2017Article
- GnRH Pulse Frequency Control of Fshb Gene Expression Is Mediated via ERK1/2 Regulation of ICER.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Insulin receptor signaling in the GnRH neuron plays a role in the abnormal GnRH pulsatility of obese female mice.PloS one · 2015Article
- GnRH pulse frequency-dependent differential regulation of LH and FSH gene expression.Molecular and cellular endocrinology · 2014Review
- Article
- The Concise Guide to PHARMACOLOGY 2013/14: G protein-coupled receptors.British journal of pharmacology · 2013Article
- Molecular mechanisms of gonadotropin-releasing hormone signaling: integrating cyclic nucleotides into the network.Frontiers in endocrinology · 2013Review
- SET protein interacts with intracellular domains of the gonadotropin-releasing hormone receptor and differentially regulates receptor signaling to cAMP and calcium in gonadotrope cells.The Journal of biological chemistry · 2013Article
- Functional significance of GnRH and kisspeptin, and their cognate receptors in teleost reproduction.Frontiers in endocrinology · 2013Article
- G proteins and autocrine signaling differentially regulate gonadotropin subunit expression in pituitary gonadotrope.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The pulsatile secretion of gonadotropin-releasing hormone (GnRH) from normal and immortalized hypothalamic GnRH neurons is highly calcium-dependent and is stimulated by cAMP. It is also influenced by agonist activation of the endogenous GnRH receptor (GnRH-R), which couples to G(q/11) as indicated by release of membrane-bound alpha(q/11) subunits and increased inositol phosphate/Ca(2+) signaling. Conversely, GnRH antagonists increase membrane-associated alpha(q/11) subunits and abolish pulsatile GnRH secretion. GnRH also stimulates cAMP production but at high concentrations has a pertussis toxin-sensitive inhibitory effect, indicative of receptor coupling to G(i). Coupling of the agonist-activated GnRH-R to both G(s) and G(i) proteins was demonstrated by the ability of nanomolar GnRH concentrations to reduce membrane-associated alpha(s) and alpha(i3) levels and of higher concentrations to diminish alpha(i3) levels. Conversely, alpha(i3) was increased during GnRH antagonist and pertussis toxin treatment, with concomitant loss of pulsatile GnRH secretion. In cholera toxin-treated GnRH neurons, decreases in alpha(s) immunoreactivity and increases in cAMP production paralleled the responses to nanomolar GnRH concentrations. Treatment with cholera toxin and 8-bromo-cAMP amplified episodic GnRH pulses but did not affect their frequency. These findings suggest that an agonist concentration-dependent switch in coupling of the GnRH-R between specific G proteins modulates neuronal Ca(2+) signaling via G(s)-cAMP stimulatory and G(i)-cAMP inhibitory mechanisms. Activation of G(i) may also inhibit GnRH neuronal function and episodic secretion by regulating membrane ion currents. This autocrine mechanism could serve as a timer to determine the frequency of pulsatile GnRH release by regulating Ca(2+)- and cAMP-dependent signaling and GnRH neuronal firing.
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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.