ArticleMolecular endocrinology (Baltimore, Md.)2016
GnRH Stimulates Peptidylarginine Deiminase Catalyzed Histone Citrullination in Gonadotrope Cells.
Article in Molecular endocrinology (Baltimore, Md.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 21 citations in OpenAlex.
- Cardiac PAD2 expression and myocardial citrullination decline with age in female mice independent of estrogen.American journal of physiology. Heart and circulatory physiology · 2025Article
- GnRH-Gonadotropes Interactions Revealed by Pituitary Single-cell Transcriptomics in Zebrafish.Endocrinology · 2024Article
- Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases.Signal transduction and targeted therapy · 2024Review
- GnRH Induces Citrullination of the Cytoskeleton in Murine Gonadotrope Cells.International journal of molecular sciences · 2024Article
- Peptidylarginine deiminase 2 regulates expression of DGCR8 affecting miRNA biogenesis in gonadotrope cells.Reproduction (Cambridge, England) · 2023Article
- Peptidylarginine deiminase enzymes and citrullinated proteins in female reproductive physiology and associated diseases†.Biology of reproduction · 2022Review
- The virtues and vices of protein citrullination.Royal Society open science · 2022Review
- Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies.Frontiers in oncology · 2022Review
- Progesterone stimulates histone citrullination to increase IGFBP1 expression in uterine cells.Reproduction (Cambridge, England) · 2021Article
- Histone citrullination: a new target for tumors.Molecular cancer · 2021Review
- Advances in the Regulation of Mammalian Follicle-Stimulating Hormone Secretion.Animals : an open access journal from MDPI · 2021Review
- Identification and Characterization of the Lactating Mouse Mammary Gland Citrullinome.International journal of molecular sciences · 2020Article
- Histone Citrullination Represses MicroRNA Expression, Resulting in Increased Oncogene mRNAs in Somatolactotrope Cells.Molecular and cellular biology · 2018Article
- Emerging insights into hypothalamic-pituitary-gonadal axis regulation and interaction with stress signalling.Journal of neuroendocrinology · 2018Review
- Peptidyl arginine deiminase 2 (Padi2) is expressed in Sertoli cells in a specific manner and regulated by SOX9 during testicular development.Scientific reports · 2018Article
- The Rheumatoid Arthritis-Associated Citrullinome.Cell chemical biology · 2018Article
- Multifaceted Targeting of the Chromatin Mediates Gonadotropin-Releasing Hormone Effects on Gene Expression in the Gonadotrope.Frontiers in endocrinology · 2018Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Peptidylarginine deiminase (PAD) enzymes convert histone tail arginine residues to citrulline resulting in chromatin decondensation. Our previous work found that PAD isoforms are expressed in female reproductive tissues in an estrous cycle-dependent fashion, but their role in the anterior pituitary gland is unknown. Thus, we investigated PAD expression and function in gonadotrope cells. The gonadotrope-derived LβT2 cell line strongly expresses PAD2 at the protein level compared with other PAD isoforms. Consistent with this, PAD2 protein expression is highest during the estrous phase of the estrous cycle and colocalizes with the LH β-subunit in the mouse pituitary. Using the GnRH agonist buserelin (GnRHa), studies in LβT2 and mouse primary gonadotrope cells revealed that 30 minutes of stimulation caused distinct puncta of PAD2 to localize in the nucleus. Once in the nucleus, GnRHa stimulated PAD2 citrullinates histone H3 tail arginine residues at sites 2, 8, and 17 within 30 minutes; however, this effect and PAD2 nuclear localization was blunted by incubation of the cells with the pan-PAD inhibitor, biphenyl-benzimidazole-Cl-amidine. Given that PAD2 citrullinates histones in gonadotropes, we next analyzed the functional consequence of PAD2 inhibition on gene expression. Our results show that GnRHa stimulates an increase in LHβ and FSHβ mRNA and that this response is significantly reduced in the presence of the PAD inhibitor biphenyl-benzimidazole-Cl-amidine. Overall, our data suggest that GnRHa stimulates PAD2-catalyzed histone citrullination in gonadotropes to epigenetically regulate gonadotropin gene expression.
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