ArticleEndocrinology2018
The Cell Type-Specific Expression of Lhcgr in Mouse Ovarian Cells: Evidence for a DNA-Demethylation-Dependent Mechanism.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 35 citations in OpenAlex.
- Trypanosoma brucei infection remodels the uterine immune environment and drives neuroendocrine dysfunction.PLoS pathogens · 2026Article
- Single-cell atlas of the mouse ovary reveals molecular drivers of aging and senescence during the estropausal transition.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular Mechanisms of Dysregulated LH and FSH Secretion in Human Reproductive Failure.Biomedicines · 2026Review
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- Multi-omics atlas of ovarian cellular and molecular responses to diabetes.Molecular metabolism · 2026Article
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- A Systematic Review and Integrated Bioinformatic Analysis on the Gene Expression of Cumulus-Oocyte Complex Following In Vitro Maturation.The Malaysian journal of medical sciences : MJMS · 2025Review
- DNA Methylation Mediates the Transcription ofCells · 2025Article
- Evaluating the impact ofJournal of the Turkish German Gynecological Association · 2024Article
- Future theranostic strategies: emerging ovarian cancer biomarkers to bridge the gap between diagnosis and treatment.Frontiers in drug delivery · 2024Review
- Luteinizing hormone receptor promotes angiogenesis in ovarian endothelial cells of Macaca fascicularis and Homo sapiens†.Biology of reproduction · 2023Article
- DNMT1-mediated lncRNA IFFD controls the follicular development via targeting GLI1 by sponging miR-370.Cell death and differentiation · 2023Article
- Biochemical alterations in the follicular fluid of bovine peri-ovulatory follicles and association with final oocyte maturation.Reproduction & fertility · 2023Article
- Porcine bile acids promote the utilization of fat and vitamin A under low-fat diets.Frontiers in nutrition · 2022Article
- Nuclear Receptors in Ovarian Function.Advances in experimental medicine and biology · 2022Article
- Large-scale DNA demethylation occurs in proliferating ovarian granulosa cells during mouse follicular development.Communications biology · 2021Article
- Cellular Heterogeneity of the Luteinizing Hormone Receptor and Its Significance for Cyclic GMP Signaling in Mouse Preovulatory Follicles.Endocrinology · 2020Article
- Exploring the roles of fecundity-related long non-coding RNAs and mRNAs in the adrenal glands of small-tailed Han Sheep.BMC genetics · 2020Article
- DNA hypermethylation in disease: mechanisms and clinical relevance.Epigenetics · 2019Review
- Developmental Programming: Contribution of Epigenetic Enzymes to Antral Follicular Defects in the Sheep Model of PCOS.Endocrinology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The luteinizing hormone receptor (LHCGR) is expressed at low levels in mural granulosa cells and cumulus cells of antral follicles and is induced dramatically in granulosa cells but not in cumulus cells by follicle-stimulating hormone (FSH). Therefore, we hypothesized that FSH not only activates transcription factors controlling Lhcgr expression but also alters other events to permit and enhance Lhcgr expression in granulosa cells but not in cumulus cells. In granulosa cells, the level of DNA methylation in the Lhcgr promoter region was significantly decreased by equine chorionic gonadotropin (eCG) in vivo. However, in cumulus cells, hypermethylation of the Lhcgr promoter remained after eCG stimulation. eCG induced estrogen production from testosterone (T) and retinoic acid (RA) synthesis in granulosa cells. When either T or RA in the presence or absence of FSH was added to granulosa cell cultures, the combined treatment with FSH and RA induced demethylation of Lhcgr-promoter region and Lhcgr expression. FSH-dependent RA synthesis was negatively regulated by coculture of granulosa cells with denuded oocytes, suggesting that oocyte-secreted factors downregulate RA production in cumulus cells where Lhcgr expression was not induced. Strikingly, treatment of cultured cumulus-oocyte complexes with a SMAD inhibitor, SB431542, significantly induced RA production, demethylation of Lhcgr-promoter region, and Lhcgr expression in cumulus cells. These results indicate the demethylation of the Lhcgr-promoter region is mediated, at least in part, by RA synthesis and is a key mechanism regulating the cell type-specific differentiation during follicular development.
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Registered trials
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