ArticleEndocrinology2013
Progesterone antagonism of neurite outgrowth depends on microglial activation via Pgrmc1/S2R.
Article in Endocrinology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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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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
23 citing papers in PubMed, 43 citations in OpenAlex.
- Anti-Inflammatory Effects of Progesterone on Human Microglia via TLR4/NLRP3 Pathway Modulation: Relevance to Drug-Resistant Epilepsy.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Microglia as candidate links between hormonal signals and neuronal circuits in polycystic ovary syndrome: evidence gaps and a research agenda.Frontiers in endocrinology · 2026Review
- Metabolic abnormalities of the cortico‑striato‑thalamo‑cortical circuit of rats with tic disorder.Molecular medicine reports · 2025Article
- Neurosteroids, Microbiota, and Neuroinflammation: Mechanistic Insights and Therapeutic Perspectives.International journal of molecular sciences · 2025Review
- Immunomodulatory Effects of Clozapine: More Than Just a Side Effect in Schizophrenia.Current neuropharmacology · 2024Review
- CmPn/CmP Signaling Networks in the Maintenance of the Blood Vessel Barrier.Journal of personalized medicine · 2023Review
- Chromosomal and gonadal factors regulate microglial sex effects in the aging brain.Brain research bulletin · 2023Review
- Article
- Depression, Estrogens, and Neuroinflammation: A Preclinical Review of Ketamine Treatment for Mood Disorders in Women.Frontiers in psychiatry · 2021Review
- PDCD4 regulates axonal growth by translational repression of neurite growth-related genes and is modulated during nerve injury responses.RNA (New York, N.Y.) · 2020Article
- PGRMC1 Inhibits Progesterone-Evoked Proliferation and CaInternational journal of molecular sciences · 2020Article
- Dual roles of astrocytes in plasticity and reconstruction after traumatic brain injury.Cell communication and signaling : CCS · 2020Review
- Article
- Sigma Receptors as Endoplasmic Reticulum Stress "Gatekeepers" and their Modulators as Emerging New Weapons in the Fight Against Cancer.Frontiers in pharmacology · 2018Review
- Progesterone receptor membrane component 1 is phosphorylated upon progestin treatment in breast cancer cells.Oncotarget · 2017Article
- The PGRMC1 Protein Level Correlates with the Binding Activity of a Sigma-2 Fluorescent Probe (SW120) in Rat Brain Cells.Molecular imaging and biology · 2016Article
- Microglia Ontology and Signaling.Frontiers in cell and developmental biology · 2016Review
- Expression of Progesterone Receptor Membrane Component 1 (PGRMC1), Progestin and AdipoQ Receptor 7 (PAQPR7), and Plasminogen Activator Inhibitor 1 RNA-Binding Protein (PAIRBP1) in Glioma Spheroids In Vitro.BioMed research international · 2016Article
- The Sigma-2 Receptor and Progesterone Receptor Membrane Component 1 are Different Binding Sites Derived From Independent Genes.EBioMedicine · 2015Article
- Comparative analysis of gonadal steroid-mediated neuroprotection after transient focal ischemia in rats: route of application and substrate composition.Journal of molecular neuroscience : MN · 2015Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Neuronal plasticity is regulated by the ovarian steroids estradiol (E2) and progesterone (P4) in many normal brain functions, as well as in acute response to injury and chronic neurodegenerative disease. In a female rat model of axotomy, the E2-dependent compensatory neuronal sprouting is antagonized by P4. To resolve complex glial-neuronal cell interactions, we used the "wounding-in-a-dish" model of neurons cocultured with astrocytes or mixed glia (microglia to astrocytes, 1:3). Although both astrocytes and mixed glia supported E2-enhanced neurite outgrowth, P4 antagonized E2-induced neurite outgrowth only with mixed glia, but not astrocytes alone. We now show that P4-E2 antagonism of neurite outgrowth is mediated by microglial expression of progesterone receptor (Pgr) membrane component 1 (Pgrmc1)/S2R, a putative nonclassical Pgr mediator with multiple functions. The P4-E2 antagonism of neurite outgrowth was restored by add-back of microglia to astrocyte-neuron cocultures. Because microglia do not express the classical Pgr, we examined the role of Pgrmc1, which is expressed in microglia in vitro and in vivo. Knockdown by siRNA-Pgrmc1 in microglia before add-back to astrocyte-neuron cocultures suppressed the P4-E2 antagonism of neurite outgrowth. Conditioned media from microglia restored the P4-E2 activity, but only if microglia were activated by lipopolysaccharide or by wounding. Moreover, the microglial activation was blocked by Pgmrc1-siRNA knockdown. These findings explain why nonwounded cultures without microglial activation lack P4 antagonism of E2-induced neurite outgrowth. We suggest that microglial activation may influence brain responses to exogenous P4, which is a prospective therapy in traumatic brain injury.
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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.