ArticleMolecular endocrinology (Baltimore, Md.)2009
Genomic and nongenomic cross talk between the gonadotropin-releasing hormone receptor and glucocorticoid receptor signaling pathways.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Injectable contraceptives differentially affect the hypothalamic-pituitary-gonadal axis and amenorrhea incidence†.Biology of reproduction · 2026Trial
- Article
- Knocking Out Sigma-1 Receptors Reveals Diverse Health Problems.Cellular and molecular neurobiology · 2022Review
- Understanding the cross-talk between mediators of infertility and COVID-19.Reproductive biology · 2021Review
- Behavioral and neurobiological effects of GnRH agonist treatment in mice-potential implications for puberty suppression in transgender individuals.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Acute slice preparation for electrophysiology increases spine numbers equivalently in the male and female juvenile hippocampus: a DiI labeling study.Journal of neurophysiology · 2019Article
- Multifaceted Targeting of the Chromatin Mediates Gonadotropin-Releasing Hormone Effects on Gene Expression in the Gonadotrope.Frontiers in endocrinology · 2018Review
- A novel non genomic glucocorticoid signaling mediated by a membrane palmitoylated glucocorticoid receptor cross talks with GnRH in gonadotrope cells.Scientific reports · 2017Article
- New Insights in Glucocorticoid Receptor Signaling-More Than Just a Ligand-Binding Receptor.Frontiers in endocrinology · 2017Review
- Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis Due to Dysfunction of the Hypothalamic Glucocorticoid Receptor in Sigma-1 Receptor Knockout Mice.Frontiers in molecular neuroscience · 2017Article
- Intrinsic and Regulated Gonadotropin-Releasing Hormone Receptor Gene Transcription in Mammalian Pituitary Gonadotrophs.Frontiers in endocrinology · 2017Review
- Glucocorticoid-independent modulation of GR activity: Implications for immunotherapy.Pharmacology & therapeutics · 2016Review
- Effects of psychological stress on male fertility.Nature reviews. Urology · 2015Review
- Minireview: Tipping the balance: ligand-independent activation of steroid receptors.Molecular endocrinology (Baltimore, Md.) · 2015Review
- Expression microarray identifies the unliganded glucocorticoid receptor as a regulator of gene expression in mammary epithelial cells.BMC cancer · 2014Article
- Lipid raft- and protein kinase C-mediated synergism between glucocorticoid- and gonadotropin-releasing hormone signaling results in decreased cell proliferation.The Journal of biological chemistry · 2014Article
- Influence of stress-induced intermediates on gonadotropin gene expression in gonadotrope cells.Molecular and cellular endocrinology · 2014Review
- Basal p38 mitogen-activated protein kinase regulates unliganded glucocorticoid receptor function in airway smooth muscle cells.American journal of respiratory cell and molecular biology · 2014Article
- The LIM domain protein nTRIP6 recruits the mediator complex to AP-1-regulated promoters.PloS one · 2014Article
- A role for glucocorticoids in stress-impaired reproduction: beyond the hypothalamus and pituitary.Endocrinology · 2013Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The GnRH receptor (GnRHR), a member of the G protein-coupled receptor family, is a central regulator of reproductive function in all vertebrates. The peptide hormone GnRH exerts its effects via binding to the GnRHR in pituitary gonadotropes. We investigated the mechanisms of regulation of transcription of the mGnRHR gene in the mouse pituitary gonadotrope L beta T2 cell line by GnRH and dexamethasone (dex). Reporter assays with transfected mGnRHR promoter show that both dex and GnRH increase transcription of the mGnRHR gene via an activating protein-1 (AP-1) site. Real-time PCR confirmed this on the endogenous mGnRHR gene, and small interfering RNA experiments revealed a requirement for the glucocorticoid receptor (GR) for both the dex and GnRH response. Chromatin immunoprecipitation (ChIP) and immunofluorescence assays provide evidence that both GnRH and dex up-regulate the GnRHR gene via nuclear translocation and interaction of the GR with the AP-1 region on the mGnRHR promoter. We show that GnRH activates the unliganded GR by rapid phosphorylation of the GR at Ser-234 in a GnRHR-dependent fashion to transactivate a GRE reporter gene in L beta T2 and COS-1 cells. Using kinase inhibitors, we established a direct link between GnRH-induced protein kinase C and MAPK activation, leading to unliganded GR phosphorylation at Ser-234 and transactivation of the glucocorticoid response element. Furthermore, we show that GnRH and dex synergistically activate the endogenous GnRHR promoter in L beta T2 cells, via a mechanism involving steroid receptor coactivator-1 recruitment to the GnRHR AP-1 region. Our results suggest a novel mechanism of rapid nongenomic cross talk between the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes via GnRHR-dependent phosphorylation and activation of the unliganded GR in response to GnRH.
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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.