ArticleEndocrinology2021
FSHB Transcription is Regulated by a Novel 5' Distal Enhancer With a Fertility-Associated Single Nucleotide Polymorphism.
Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 4 of them syntheses that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 4 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Genome-wide association study meta-analysis of dizygotic twinning illuminates genetic regulation of female fecundity.Human reproduction (Oxford, England) · 2024Pooled it
- New insights into the (epi)genetics of twinning.Human reproduction (Oxford, England) · 2024Pooled it
- The landscape of GWAS validation; systematic review identifying 309 validated non-coding variants across 130 human diseases.BMC medical genomics · 2022Pooled it
- A multi-level investigation of the genetic relationship between endometriosis and ovarian cancer histotypes.Cell reports. Medicine · 2022Pooled it
- From Gene Function to Precision Intervention: CRISPR/Cas9 and Stem Cell-Based Strategies as Emerging Disease-Modifying Approaches in PMOS.Stem cell reviews and reports · 2026Review
- Consensus Pituitary Atlas, a scalable resource for annotation, novel marker discovery, and analyses in mouse pituitary gland research.Cell reports · 2026Article
- Regulatory risk loci link disrupted androgen response to the pathophysiology of polycystic ovary syndrome.Journal of the Endocrine Society · 2026Article
- Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.Endocrinology · 2026Article
- Accessibility at a primed distal Fshb-Kcna4 super-enhancer is facilitated by Foxl2 during gonadotrope differentiation.Endocrinology · 2026Article
- Molecular Mechanisms of Dysregulated LH and FSH Secretion in Human Reproductive Failure.Biomedicines · 2026Review
- C/EBPβ dictates postmenopausal FSHβ transcription and blockade of AEP/C/EBPβ pathway alleviates osteoporosis.Bone research · 2026Article
- Regulation of murine follicle-stimulating hormone β subunit transcription by newly identified enhancers.bioRxiv : the preprint server for biology · 2025Article
- Gene regulatory activity associated with polycystic ovary syndrome revealed DENND1A-dependent testosterone production.Nature communications · 2025Article
- A Point Mutation in an Otherwise Dispensable Upstream Fshb Enhancer Moderately Impairs Fertility in Female Mice.Endocrinology · 2025Article
- An i-motif-regulated enhancer, eRNA and adjacent lncRNA affect Lhb expression through distinct mechanisms in a sex-specific context.Cellular and molecular life sciences : CMLS · 2024Article
- A Common Genetic Factor Underlies Genetic Risk for Gynaecological and Reproductive Disorders and Is Correlated with Risk to Depression.Neuroendocrinology · 2023Article
- Deconstructing a Syndrome: Genomic Insights Into PCOS Causal Mechanisms and Classification.Endocrine reviews · 2022Article
- Steroidogenic Factor 1 Regulates Transcription of the Inhibin B Coreceptor in Pituitary Gonadotrope Cells.Endocrinology · 2022Article
- A GWAS in Idiopathic/Unexplained Infertile Men Detects a Genomic Region Determining Follicle-Stimulating Hormone Levels.The Journal of clinical endocrinology and metabolism · 2022Article
- Enhancing Gonadotrope Gene Expression Through Regulatory lncRNAs.Endocrinology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The pituitary gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone, signal the gonads to regulate male and female fertility. FSH is critical for female fertility as it regulates oocyte maturation, ovulation, and hormone synthesis. Multiple genome-wide association studies (GWAS) link a 130 Kb locus at 11p14.1, which encompasses the FSH beta-subunit (FSHB) gene, with fertility-related traits that include polycystic ovary syndrome, age of natural menopause, and dizygotic twinning. The most statistically significant single nucleotide polymorphism from several GWAS studies (rs11031006) resides within a highly conserved 450 bp region 26 Kb upstream of the human FSHB gene. Given that sequence conservation suggests an important biological function, we hypothesized that the region could regulate FSHB transcription. In luciferase assays, the conserved region enhanced FSHB transcription and gel shifts identified a binding site for Steroidogenic factor 1 (SF1) contributing to its function. Analysis of mouse pituitary single-cell ATAC-seq demonstrated open chromatin at the conserved region exclusive to a gonadotrope cell-type cluster. Additionally, enhancer-associated histone markers were identified by immunoprecipitation of chromatin from mouse whole pituitary and an immortalized mouse gonadotrope-derived LβT2 cell line at the conserved region. Furthermore, we found that the rs11031006 minor allele upregulated FSHB transcription via increased SF1 binding to the enhancer. All together, these results identify a novel upstream regulator of FSHB transcription and indicate that rs11031006 can modulate FSH levels.
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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 Socratic graph.