Affinage

FSHR

Follicle-stimulating hormone receptor · UniProt P23945

Length
695 aa
Mass
78.2 kDa
Annotated
2026-04-28
100 papers in source corpus 22 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FSHR is a G protein-coupled receptor that transduces follicle-stimulating hormone signaling primarily through the Gαs/cAMP/PKA/CREB cascade, with additional engagement of β-arrestin, PI3K/AKT, and mTOR-HIF1α pathways, to drive folliculogenesis, granulosa cell survival, estradiol biosynthesis, and fetal placental angiogenesis (PMID:20086006, PMID:29715497, PMID:37733588, PMID:34925235). FSHR transcription in Sertoli and granulosa cells depends on USF1/2 binding to a promoter E-box and is modulated by an intronic silencer occupied by OCT-1, by upstream signals including androgens, BMP15 (via Smad/p38/USF1), TGF-β/SMAD4-mediated suppression of miR-143, and metabolic regulators such as TRIB3/Akt/GSK3β (PMID:9773974, PMID:15817654, PMID:16641147, PMID:31079267, PMID:27882941, PMID:34503515). Receptor function is further regulated by ligand glycoform-dependent oligomerization dynamics, scaffolding interactions with 14-3-3τ, APPL1/2, and FOXO1a, and by post-translational tyrosine nitration at Y626 that impairs surface trafficking and downstream Akt-FoxO3a survival signaling (PMID:34925235, PMID:15196694, PMID:17030088, PMID:31097679). Loss-of-function mutations in FSHR, including the p.R59X nonsense variant, cause primary ovarian insufficiency by abolishing cAMP signaling and arresting folliculogenesis (PMID:29157895).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Identifying the cis-regulatory logic of FSHR transcription established that USF1/2 binding to a promoter E-box is essential for FSHR expression in Sertoli cells, answering how cell-type-specific transcription is initiated.

    Evidence Deletion/block-replacement mutagenesis and EMSA with USF antibody supershift in MSC-1 line and primary Sertoli cells

    PMID:9773974

    Open questions at the time
    • USF1/2 requirement not tested in granulosa cells at this point
    • Chromatin context (histone modifications) not addressed
    • Distal enhancer contributions unknown
  2. 2004 High

    Discovery of 14-3-3τ as an FSH-dependent interactor of FSHR intracellular loops revealed that scaffolding proteins modulate receptor signaling output, providing the first non-G-protein binding partner of FSHR.

    Evidence Yeast two-hybrid, co-immunoprecipitation in FSHR-expressing HEK293 cells, and cAMP functional assay

    PMID:15196694

    Open questions at the time
    • Physiological relevance in granulosa/Sertoli cells not tested
    • Mechanism by which 14-3-3τ attenuates cAMP unclear
    • Whether other 14-3-3 isoforms contribute is unknown
  3. 2005 High

    Identification of an intronic silencer element (DHS3) bound by OCT-1 in non-expressing cells explained how FSHR transcription is repressed outside the gonad, with GATA-1 counteracting this silencing in Sertoli cells.

    Evidence DNase I hypersensitivity mapping, ChIP at endogenous locus, EMSA, and functional transfection with mutagenesis

    PMID:15817654

    Open questions at the time
    • Whether OCT-1/GATA balance shifts during development not addressed
    • Role of DHS3 in granulosa cells unknown
  4. 2006 High

    Multiple discoveries in 2006 expanded the regulatory landscape: androgens acting through the androgen receptor upregulate FSHR mRNA in granulosa cells, APPL1/2 and FOXO1a form distinct scaffolding networks on the receptor, and distal conserved elements beyond a 413 kb transgene are needed for correct in vivo expression.

    Evidence Primary bovine granulosa cells with selective antagonists (bicalutamide/ICI); co-IP domain mapping in HEK293; YAC transgenic mice with comparative genomics

    PMID:16641147 PMID:17030088 PMID:17097219

    Open questions at the time
    • Androgen receptor binding site on FSHR promoter not identified
    • APPL1/2 functional contribution to FSH signaling not tested
    • Distal regulatory elements not validated by targeted deletion in vivo
  5. 2010 High

    Adenoviral FSHR rescue in Fshr-knockout mice proved that FSHR expression in granulosa cells is both required and sufficient for progression of folliculogenesis beyond the primary stage, establishing the receptor's indispensable in vivo role.

    Evidence In vivo adenoviral gene delivery into Fshr−/− mouse ovaries with histological and hormonal phenotyping

    PMID:20086006

    Open questions at the time
    • Rescue was transient; long-term fertility not assessed
    • Whether FSHR in theca or other ovarian cells contributes remains untested
  6. 2013 Medium

    SMAD3 was placed upstream of FSHR transcription in granulosa cells, linking TGF-β superfamily signaling to receptor abundance and downstream PKA activity.

    Evidence SMAD3 overexpression and RNAi in primary rat granulosa cells with Western blot for FSHR/PKA and estrogen measurement

    PMID:23690627

    Open questions at the time
    • Direct SMAD3 binding to FSHR promoter not demonstrated
    • Contribution relative to BMP/Smad1/5/8 pathway unclear
  7. 2014 High

    Discovery of exon 2/3-skipped FSHR splice variants that abolish cAMP signaling linked receptor isoform diversity to poor ovarian response in IVF patients, connecting alternative splicing to clinical phenotype.

    Evidence RT-PCR from cumulus cells of IVF patients; reconstitution of splice variants in HEK293 cells with cAMP assay

    PMID:24670307

    Open questions at the time
    • Mechanism driving exon skipping unknown
    • Prevalence in general population not determined
    • Dominant-negative effects on wild-type receptor not tested
  8. 2016 High

    Convergent 2016 studies demonstrated biased signaling pharmacology and upstream miRNA-mediated regulation: negative allosteric modulators showed differential antagonism of cAMP vs. β-arrestin pathways, TGF-β/SMAD4 was shown to maintain FSHR levels by suppressing miR-143, and the N680S polymorphism was directly linked to reduced cAMP output in patient granulosa cells.

    Evidence NAM profiling in HEK293 and Leydig cells; miR-143 OE/inhibition with SMAD4 ChIP in porcine granulosa cells; cAMP measurement in genotype-stratified human granulosa cells from IVF

    PMID:26769719 PMID:27424143 PMID:27882941

    Open questions at the time
    • Biased agonism in vivo untested
    • miR-143 regulation of FSHR not confirmed in human cells
    • N680S structural basis for reduced signaling unknown
  9. 2017 High

    Loss-of-function mutations (p.R59X nonsense and R634H cytoplasmic tail) established that both receptor protein expression and proper surface trafficking are essential for FSH-induced cAMP production, with p.R59X causing primary ovarian insufficiency.

    Evidence Sanger sequencing, Western blot, and cAMP assay in transfected cells for both mutations; ovarian histology for R59X

    PMID:28446136 PMID:29157895

    Open questions at the time
    • R634H associated clinical phenotype from single case only
    • Whether R634H affects β-arrestin or other non-cAMP pathways untested
  10. 2018 High

    Fetal FSHR was shown to be required for placental labyrinth angiogenesis, extending FSHR function beyond the gonad to vascular biology during development.

    Evidence Fshr null fetuses in wild-type dams with quantitative morphometric analysis of placental labyrinths

    PMID:29715497

    Open questions at the time
    • Downstream angiogenic signaling pathway not identified
    • Whether endothelial FSHR directly activates VEGF or other angiogenic factors unknown
  11. 2019 High

    Three 2019 studies resolved distinct post-transcriptional and post-translational control mechanisms: BMP15 induces FSHR via Smad/p38-USF1 chromatin remodeling, peroxynitrite-mediated Y626 nitration sequesters FSHR intracellularly, and TRIB3/Akt/GSK3β links metabolic stress to FSHR downregulation.

    Evidence ChIP for histone marks and USF1/2 at FSHR promoter in HGrC1 cells; Y626A mutagenesis with immunofluorescence and Akt/FoxO3a signaling in KGN cells; TRIB3 siRNA with Akt inhibitor rescue in primary human granulosa cells

    PMID:31079267 PMID:31097679 PMID:34503515

    Open questions at the time
    • In vivo relevance of Y626 nitration not established
    • BMP15-USF1 axis not validated in primary human follicles
    • TRIB3 mechanism at FSHR promoter (direct vs. indirect) unclear
  12. 2021 High

    Super-resolution imaging revealed that FSH glycoform composition controls FSHR oligomerization dynamics — hypo-glycosylated FSH dissociates oligomers into monomers correlating with higher cAMP, while β-arrestin-biased ligands promote homomerization — providing a structural basis for ligand-biased signaling.

    Evidence PD-PALM super-resolution imaging of FSHR in HEK293 cells with defined FSH glycoforms and cAMP ELISA

    PMID:34925235

    Open questions at the time
    • Oligomerization dynamics not assessed in primary granulosa/Sertoli cells
    • Structural interface mediating oligomer-monomer transition undefined
    • Physiological ratio of FSH glycoforms in follicular fluid not linked to receptor state
  13. 2023 Medium

    FSHR was placed at the apex of an mTOR-HIF1α survival axis in granulosa cells, explaining how FSH signaling enables follicles to escape AMPK-driven atresia and linking receptor activation to metabolic control of follicle fate.

    Evidence Single-cell transcriptomics of mouse granulosa cells with functional validation using pathway inhibitors and HIF1 loss-of-function

    PMID:37733588

    Open questions at the time
    • HIF1α target genes mediating survival not fully identified
    • Whether this axis operates in human follicles untested
    • Interaction with BMP15/TRIB3 regulatory inputs not examined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the structural basis of FSHR oligomerization and its transition upon ligand binding, the in vivo significance of post-translational modifications such as Y626 nitration, the identity of downstream angiogenic effectors of placental FSHR, and how the multiple transcriptional inputs (USF, SMAD, androgen receptor, miR-143) are integrated in a follicle-stage-specific manner.
  • No high-resolution structure of full-length FSHR in active oligomeric state
  • No in vivo confirmation that Y626 nitration regulates fertility
  • Placental FSHR downstream signaling cascade undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1474165 Reproduction 3 R-HSA-1266738 Developmental Biology 2
Partners
AKT2APPL1APPL2ARRB2FOXO1USF1USF2YWHAQ

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 FSHR interacts with the adapter protein 14-3-3tau via its first and second intracellular loops; this interaction is FSH-dependent and over-expression of 14-3-3tau modestly decreases FSH-induced cAMP accumulation, implicating 14-3-3tau in regulation of FSHR signaling. Yeast two-hybrid screen (iL1-iL2 bait vs. human ovarian cDNA library), co-immunoprecipitation in HEK293 cells stably expressing FSHR, functional cAMP assay with 14-3-3tau over-expression Molecular and cellular endocrinology High 15196694
2006 FSHR interacts with APPL1, APPL2, Akt2, and FOXO1a, organizing them into distinct scaffolding networks; APPL1 and APPL2 associate with each other via the N-terminal BAR domain of APPL1, but APPL2 does not bind Akt2 (first documented functional difference between APPL1 and APPL2), and FOXO1a does not associate with either APPL protein. Co-immunoprecipitation in HEK293 cells, interaction mapping with domain deletion constructs Molecular and cellular endocrinology Medium 17030088
1998 FSHR promoter activity in Sertoli cells requires multiple elements including a critical E-box (CACGTG); USF1 and USF2 are the primary proteins binding this E-box, and mutation of core or flanking E-box sequences abolishes promoter function. A second E-box-binding complex cross-reactive with USF antibodies is present only in primary Sertoli cells. Transient transfection of deletion/block-replacement mutants in Sertoli cell line (MSC-1) and primary Sertoli cells; EMSA with USF antibodies Molecular endocrinology High 9773974
2005 Fshr transcription is silenced by a DNase I hypersensitive site (DHS3) in the first intron; OCT-1 binds site 7 within DHS3 in non-expressing myoid cells to repress transcription, while GATA-1 binds the same site predominantly in Sertoli cells and attenuates silencing. ChIP confirmed OCT-1 occupancy at the endogenous locus. DNase I hypersensitivity mapping, transient transfection of DHS3 constructs, EMSA, chromatin immunoprecipitation (ChIP) Molecular endocrinology High 15817654
2006 Distal regulatory elements outside a 413 kb YAC transgene are required for correct spatiotemporal Fshr expression in vivo; evolutionarily conserved regions (ECR4, ECR5) outside this region showed differential transcriptional activity in expressing vs. non-expressing cells. YAC transgenic mice (RT-PCR for transgene expression), comparative genomics, transient transfection of ECRs Molecular and cellular endocrinology Medium 17097219
2006 FSHR mRNA in bovine granulosa cells is specifically upregulated by androgens (testosterone and DHT) through the androgen receptor, not by estradiol; this was shown by bicalutamide blocking T/DHT effects on FSHR but not CYP19A1, while ICI 182,780 blocked estrogen effects on CYP19A1 but not FSHR. Primary bovine granulosa cell culture, steroid dose-response and duration experiments, selective receptor antagonists (bicalutamide, ICI 182,780), quantitative mRNA measurement Biology of reproduction High 16641147
2010 Intra-ovarian injection of adenovirus expressing human FSHR into FORKO (Fshr knockout) mice restored FSH responsiveness, reinitiated folliculogenesis beyond the primary stage, increased estrogen 2–3-fold, and decreased FSH by 50%, demonstrating that FSHR expression in granulosa cells is required and sufficient for folliculogenesis progression. In vivo adenoviral gene delivery into Fshr-/- mice, histological evaluation of follicle stages, serum hormone ELISA, vaginal cytology Molecular human reproduction High 20086006
2014 Alternative skipping of FSHR exon 2 or exon 3 produces receptor variants that fail to initiate cAMP signaling upon FSH stimulation despite high ligand doses, and these splice variants are exclusive to low ovarian responders undergoing IVF. RT-PCR of cumulus cells from IVF patients, identification of splice variants, transfection of full-length and variant constructs into HEK293 cells with cAMP assay Molecular human reproduction High 24670307
2017 A novel homozygous nonsense mutation in FSHR (p.R59X, exon 2) causes primary ovarian insufficiency by abolishing full-length receptor protein expression and eliminating FSH-induced cAMP signaling, arresting folliculogenesis. Sanger sequencing, Western blotting for FSHR protein, cAMP assay in cells transfected with wild-type vs. mutant FSHR, ovarian histology Fertility and sterility High 29157895
2017 A novel FSHR cytoplasmic tail mutation (R634H, c.1901G>A) does not confer constitutive activity but reduces cell surface expression of the receptor and decreases FSH-stimulated cAMP production. Sanger sequencing, functional cAMP assay, cell surface expression analysis BMC medical genetics Medium 28446136
2019 BMP15 induces FSHR expression in human granulosa cells through both Smad1/5/8 (canonical) and non-Smad (p38 MAPK → USF1 phosphorylation) pathways, leading to increased histone acetyltransferase activity, histone modifications at the FSHR promoter, and enhanced USF1/2 binding, which ultimately increases CYP19A1 expression and estradiol production. Immortalized human granulosa (HGrC1) cells stimulated with BMP15 ± inhibitors (LDN193189, SB203580); Western blot for Smad and MAPK phosphorylation; HAT activity assay; ChIP for histone modifications and USF1/2 binding; FSHR and CYP19A1 mRNA/protein measurement; estradiol ELISA Journal of assisted reproduction and genetics High 31079267
2019 Tyrosine nitration of FSHR by peroxynitrite sequesters the receptor in the cytoplasm and promotes its proteasomal degradation; Y626 was identified as the critical nitrated residue required for intracellular trafficking to the cell surface, and peroxynitrite-mediated FSHR mislocalization impairs FSH-induced Akt-FoxO3a survival signaling in granulosa cells. Site-directed mutagenesis of four nitrated tyrosine residues (Y626A and others), immunofluorescence for FSHR localization, peroxynitrite treatment of KGN cells, Akt/FoxO3a phosphorylation by Western blot, apoptosis assay Aging High 31097679
2021 Differential FSH glycosylation modulates FSHR oligomerization and downstream cAMP production: hypo-glycosylated FSH21/18 and high-dose eFSH rapidly dissociate FSHR oligomers into monomers (correlating with higher cAMP), while fully glycosylated FSH24 shows slower kinetics; a β-arrestin-biased agonist (truncated eLHβ + dg-eLHα) promotes FSHR homomerization. Super-resolution imaging (PD-PALM) of FSHR complexes in HEK293 cells; comparison of FSH glycoforms (FSH21/18 vs. FSH24) at multiple concentrations and time points; cAMP ELISA Frontiers in endocrinology High 34925235
2016 FSHR negative allosteric modulators ADX68692 and ADX68693 display biased antagonism at both FSHR and the closely related LH/CGR: ADX68693 more potently inhibits hCG-induced cAMP and β-arrestin 2 recruitment, and differentially suppresses progesterone and testosterone production in Leydig cells, demonstrating that cAMP and β-arrestin pathways contribute differently to FSHR- vs. LH/CGR-mediated steroidogenesis. cAMP assay in HEK293 cells and mLTC-1/rat primary Leydig cells; β-arrestin 2 recruitment assay; progesterone and testosterone ELISA; pharmacological profiling with two NAMs Molecular and cellular endocrinology High 27424143
2016 Granulosa cells from women homozygous for the FSHR N680S (AA) variant show lower intracellular cAMP responses to Follitropin alpha stimulation compared to women with other genotypes, providing a direct functional cellular correlate of this polymorphism. Granulosa cells isolated by flow cytometry from IVF patients, stimulated with FSH; cAMP and IP3 measured by ELISA; genotype-stratified comparison Human reproduction Medium 26769719
2018 Deletion of fetoplacental FSHR (Fshr null fetuses in Fshr wild-type dams) significantly reduces the proportion of placenta composed of labyrinth and decreases fetal vessel angiogenesis within the labyrinth, demonstrating that FSHR signaling in fetal vascular endothelium is required for placental angiogenesis. Fshr null mice with genotype-controlled pregnancies, quantitative morphometric analysis of placental labyrinths at mid-gestation Molecular and cellular endocrinology High 29715497
2020 FSHR ablation in mice (Fshr-/- with ovariectomy) induces depression-like behaviors associated with severe oxidative stress in the brain due to reduced GCLm (glutathione synthesis) and G6PD (NADPH pathway); administration of NAC rescued the phenotype. FSH dose-dependently increased GCLm and G6PD and decreased ROS in neurons, indicating FSHR signaling maintains neuronal redox balance. Fshr-/- ovariectomized mice, behavioral tests, ROS measurement, Western blot for GCLm/G6PD; N2a neuroblastoma cells treated with FSH; NAC rescue Acta pharmacologica Sinica Medium 32203083
2023 FSHR activates mTOR-HIF1α signaling in granulosa cells to promote follicle survival; HIF1 activation is essential for follicle growth downstream of FSH, while AMPK activation (energy shortage) drives atresia, and the FSHR-mTOR-HIF1 axis allows follicles to escape AMPK-induced atresia. Single-cell transcriptomic atlas of mouse granulosa cells, functional validation in granulosa cell models with pathway inhibitors and activators, HIF1 loss-of-function Cell reports Medium 37733588
2019 TRIB3 upregulated by high free fatty acids reduces FSHR expression in human granulosa cells through the Akt/GSK3β pathway; TRIB3 knockdown reversed FFA-induced FSHR downregulation and restored estradiol production, and Akt inhibition in TRIB3-knockdown cells increased p-GSK3β but elevated FSHR expression, revealing TRIB3→Akt→GSK3β as a regulatory axis controlling FSHR. Primary human granulosa cells and KGN cells, palmitic acid treatment, TRIB3 siRNA knockdown, Western blot for p-Akt/p-GSK3β/TRIB3/FSHR, estradiol ELISA, p-Akt inhibitor treatment Reproductive biology and endocrinology Medium 34503515
2023 Paeoniflorin restores estradiol synthesis in ovarian granulosa cells via activation of the FSHR/cAMP/PKA/CREB signaling pathway; siRNA knockdown of FSHR and an FSHR antagonist both abolished paeoniflorin's effects, placing FSHR upstream of cAMP/PKA/CREB and aromatase induction. Cisplatin-induced DOR mouse model, KGN cells with siRNA-FSHR knockdown and FSHR antagonist, cAMP/PKA/CREB Western blot, estradiol and aromatase measurement Molecules Medium 38138611
2013 SMAD3 overexpression in rat granulosa cells promotes estrogen production and proliferation while inhibiting apoptosis, and these effects are associated with increased FSHR and PKA expression, placing SMAD3 upstream of FSHR-mediated cAMP/PKA signaling in granulosa cell function. Primary rat granulosa cells with Smad3 overexpression and RNAi knockdown, Western blot for FSHR/PKA/cyclin D2/PCNA, estrogen ELISA, flow cytometry for cell cycle and apoptosis Reproduction Medium 23690627
2016 TGF-β/SMAD4 signaling prevents granulosa cell apoptosis and follicular atresia in part by suppressing miR-143, which directly targets FSHR; miR-143 overexpression reduces FSHR levels and downstream PKA and AKT/p-AKT signaling, while activated TGF-β signaling rescues miR-143-induced FSHR downregulation and apoptosis. pGC knockdown of FSHR, miR-143 overexpression/inhibition, SMAD4 chromatin binding assay (luciferase/ChIP for miR-143 promoter), Western blot for PKA/AKT/p-AKT, apoptosis assay; in vivo follicular atresia model in pigs Cell death & disease High 27882941

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Hormone-refractory prostate cancer cells express functional follicle-stimulating hormone receptor (FSHR). The Journal of urology 112 10022736
2016 TGF-β signaling controls FSHR signaling-reduced ovarian granulosa cell apoptosis through the SMAD4/miR-143 axis. Cell death & disease 111 27882941
2009 The G protein-coupled receptor FSHR-1 is required for the Caenorhabditis elegans innate immune response. Proceedings of the National Academy of Sciences of the United States of America 103 19196974
2009 Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome. Journal of assisted reproduction and genetics 94 19387820
2012 Combined effects of the variants FSHB -211G>T and FSHR 2039A>G on male reproductive parameters. The Journal of clinical endocrinology and metabolism 91 22791757
2006 Distinct regulation by steroids of messenger RNAs for FSHR and CYP19A1 in bovine granulosa cells. Biology of reproduction 91 16641147
2012 FSH stimulates lipid biosynthesis in chicken adipose tissue by upregulating the expression of its receptor FSHR. Journal of lipid research 89 22345708
2010 FSHR gene polymorphisms influence bone mineral density and bone turnover in postmenopausal women. European journal of endocrinology 82 20335500
2006 APPL1, APPL2, Akt2 and FOXO1a interact with FSHR in a potential signaling complex. Molecular and cellular endocrinology 78 17030088
2019 Upregulation of FSHR and PCNA by administration of coenzyme Q10 on cyclophosphamide-induced premature ovarian failure in a mouse model. Journal of biochemical and molecular toxicology 72 31557371
2019 Follicle Stimulating Hormone Receptor (FSHR) Polymorphisms and Polycystic Ovary Syndrome (PCOS). Frontiers in endocrinology 71 30809190
2008 Mutations and polymorphisms of the FSH receptor (FSHR) gene: clinical implications in female fecundity and molecular biology of FSHR protein and gene. Obstetrical & gynecological survey 69 19017414
2021 An overview of FSH-FSHR biology and explaining the existing conundrums. Journal of ovarian research 65 34717708
2010 Two FSHR variants, haplotypes and meta-analysis in Chinese women with premature ovarian failure and polycystic ovary syndrome. Molecular genetics and metabolism 60 20399696
2011 Influence of follicle-stimulating hormone receptor (FSHR) Ser680Asn polymorphism on ovarian function and in-vitro fertilization outcome: a meta-analysis. Molecular genetics and metabolism 59 21546300
2016 Combined assessment of polymorphisms in the LHCGR and FSHR genes predict chance of pregnancy after in vitro fertilization. Human reproduction (Oxford, England) 55 26769719
1998 Multiple promoter elements contribute to activity of the follicle-stimulating hormone receptor (FSHR) gene in testicular Sertoli cells. Molecular endocrinology (Baltimore, Md.) 51 9773974
2013 Research resource: small RNA-seq of human granulosa cells reveals miRNAs in FSHR and aromatase genes. Molecular endocrinology (Baltimore, Md.) 50 23660593
2019 Extragonadal FSHR Expression and Function-Is It Real? Frontiers in endocrinology 48 30778333
2000 Characterization of two fly LGR (leucine-rich repeat-containing, G protein-coupled receptor) proteins homologous to vertebrate glycoprotein hormone receptors: constitutive activation of wild-type fly LGR1 but not LGR2 in transfected mammalian cells. Endocrinology 47 11089539
2013 Association of allelic combinations of FSHR gene polymorphisms with ovarian response. Reproductive biomedicine online 46 23953588
2013 The combination of genetic variants of the FSHB and FSHR genes affects serum FSH in women of reproductive age. Human reproduction (Oxford, England) 45 23504007
2012 Study in 1790 Baltic men: FSHR Asn680Ser polymorphism affects total testes volume. Andrology 45 23413141
2007 The C. elegans glycopeptide hormone receptor ortholog, FSHR-1, regulates germline differentiation and survival. Current biology : CB 44 17276913
2008 The gonadotropin receptors FSH-R and LH-R of Atlantic halibut (Hippoglossus hippoglossus)--2. Differential follicle expression and asynchronous oogenesis. General and comparative endocrinology 41 18377904
2019 FSHR-1/GPCR Regulates the Mitochondrial Unfolded Protein Response in Caenorhabditis elegans. Genetics 40 31801834
2017 A novel homozygous mutation in the FSHR gene is causative for primary ovarian insufficiency. Fertility and sterility 40 29157895
2023 Iron overload modulates follicular microenvironment via ROS/HIF-1α/FSHR signaling. Free radical biology & medicine 39 36638901
2015 Flow cytometric analysis of FSHR, BMRR1B, LHR and apoptosis in granulosa cells and ovulation rate in merino sheep. Reproduction (Cambridge, England) 38 25948249
2014 Reproductive physiology in young men is cumulatively affected by FSH-action modulating genetic variants: FSHR -29G/A and c.2039 A/G, FSHB -211G/T. PloS one 37 24718625
2011 Differential regulation of gonadotropin receptors (fshr and lhcgr) by estradiol in the zebrafish ovary involves nuclear estrogen receptors that are likely located on the plasma membrane. Endocrinology 37 21878512
2008 A distribution of two SNPs in exon 10 of the FSHR gene among the women with a diminished ovarian reserve in Ukraine. Journal of assisted reproduction and genetics 37 19031050
2004 Human follitropin receptor (FSHR) interacts with the adapter protein 14-3-3tau. Molecular and cellular endocrinology 36 15196694
2015 Polymorphisms of the Ovine BMPR-IB, BMP-15 and FSHR and Their Associations with Litter Size in Two Chinese Indigenous Sheep Breeds. International journal of molecular sciences 35 25993301
2014 Ala307Thr and Asn680Ser polymorphisms of FSHR gene in human reproduction outcomes. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 35 25322982
2021 The effect of polymorphisms in FSHR and FSHB genes on ovarian response: a prospective multicenter multinational study in Europe and Asia. Human reproduction (Oxford, England) 34 33889959
2008 Multilocus analyses reveal involvement of the ESR1, ESR2, and FSHR genes in migraine. Headache 33 19093296
2019 Biased Signaling and Allosteric Modulation at the FSHR. Frontiers in endocrinology 32 30930853
2016 Follicle-Stimulating Hormone Receptor (FSHR): A Promising Tool in Oncology? Molecular diagnosis & therapy 32 27392476
2015 Functional role of the heterodimeric glycoprotein hormone, GPA2/GPB5, and its receptor, LGR1: An invertebrate perspective. General and comparative endocrinology 32 26704853
2010 Toward gene therapy of premature ovarian failure: intraovarian injection of adenovirus expressing human FSH receptor restores folliculogenesis in FSHR(-/-) FORKO mice. Molecular human reproduction 32 20086006
2008 Molecular characterization and quantification of the gonadotropin receptors FSH-R and LH-R from Atlantic cod (Gadus morhua). General and comparative endocrinology 32 18992749
2016 Profiling of FSHR negative allosteric modulators on LH/CGR reveals biased antagonism with implications in steroidogenesis. Molecular and cellular endocrinology 31 27424143
2014 Association between FSHR polymorphisms and polycystic ovary syndrome among Chinese women in north China. Journal of assisted reproduction and genetics 31 24390680
2014 Pilot study of a novel (18)F-labeled FSHR probe for tumor imaging. Molecular imaging and biology 30 24389931
2019 Molecular mechanism of FSHR expression induced by BMP15 in human granulosa cells. Journal of assisted reproduction and genetics 29 31079267
2010 FSHR single nucleotide polymorphism frequencies in proven fathers and infertile men in Southeast Turkey. Journal of biomedicine & biotechnology 28 20454649
2017 A Novel Homozygous Missense FSHR Variant Associated with Hypergonadotropic Hypogonadism in Two Siblings from a Brazilian Family. Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation 27 28591755
2019 Correlation of the Aryl Hydrocarbon Receptor with FSHR in Ovarian Cancer Patients. International journal of molecular sciences 25 31212758
2014 Follicle-stimulating hormone receptor (FSHR) alternative skipping of exon 2 or 3 affects ovarian response to FSH. Molecular human reproduction 25 24670307
2014 Evaluating influence of the genotypes in the follicle-stimulating hormone receptor (FSHR) Ser680Asn (rs6166) polymorphism on poor and hyper-responders to ovarian stimulation: a meta-analysis. Journal of ovarian research 25 25526787
2013 Association study between FSHR Ala307Thr and Ser680Asn variants and polycystic ovary syndrome (PCOS) in Northern Chinese Han women. Journal of assisted reproduction and genetics 25 23536150
2006 Developmental changes of FSH-R, LH-R, ER-beta and GnRH-I expression in the ovary of prepubertal ducks (Anas platyrhynchos). Animal reproduction science 24 16989964
2023 FSHR-mTOR-HIF1 signaling alleviates mouse follicles from AMPK-induced atresia. Cell reports 23 37733588
2017 First mutation in the FSHR cytoplasmic tail identified in a non-pregnant woman with spontaneous ovarian hyperstimulation syndrome. BMC medical genetics 23 28446136
2014 Silencing D. melanogaster lgr1 impairs transition from larval to pupal stage. General and comparative endocrinology 23 25157788
2011 Polymorphism of 5' regulatory region of ovine FSHR gene and its association with litter size in Small Tail Han sheep. Molecular biology reports 23 21725846
2017 The susceptibility of FSHB -211G > T and FSHR G-29A, 919A > G, 2039A > G polymorphisms to men infertility: an association study and meta-analysis. BMC medical genetics 22 28764642
2021 Differential FSH Glycosylation Modulates FSHR Oligomerization and Subsequent cAMP Signaling. Frontiers in endocrinology 21 34925235
2021 Endogenous, tissue-resident stem/progenitor cells in gonads and bone marrow express FSHR and respond to FSH via FSHR-3. Journal of ovarian research 20 34717703
2020 Target prediction and validation of microRNAs expressed from FSHR and aromatase genes in human ovarian granulosa cells. Scientific reports 20 32042028
2012 The ovarian response to standard gonadotrophin stimulation depends on FSHR, SHBG and CYP19 gene synergism. Journal of assisted reproduction and genetics 20 22915343
2012 Elevated level of 17β-estradiol is associated with overexpression of FSHR, CYP19A1, and CTNNB1 genes in porcine ovarian follicles after prenatal and neonatal flutamide exposure. Theriogenology 20 23043943
2009 Modulation of ovarian structure and abdominal obesity in curcumin- and flutamide-treated aging FSH-R haploinsufficient mice. Reproductive sciences (Thousand Oaks, Calif.) 20 19304795
2019 Sequence variants in FSHR and CYP19A1 genes and the ovarian response to controlled ovarian stimulation. Fertility and sterility 19 31371045
2018 FSHR Trans-Activation and Oligomerization. Frontiers in endocrinology 19 30619090
2012 Assessment of FSHR variants and antimüllerian hormone in infertility patients with a reduced ovarian response to gonadotropin stimulation. Fertility and sterility 19 22401810
2012 The effects of epidermal growth factor (EGF) on the in vitro development of isolated goat secondary follicles and the relative mRNA expression of EGF, EGF-R, FSH-R and P450 aromatase in cultured follicles. Research in veterinary science 19 23270918
2019 Effects of FSHR polymorphisms on premature ovarian insufficiency in human beings: a meta-analysis. Reproductive biology and endocrinology : RB&E 18 31629411
2005 Silencing of Fshr occurs through a conserved, hypersensitive site in the first intron. Molecular endocrinology (Baltimore, Md.) 18 15817654
2022 A mAb against surface-expressed FSHR engineered to engage adaptive immunity for ovarian cancer immunotherapy. JCI insight 16 36509287
2020 Ultrasound Molecular Imaging of Renal Cell Carcinoma: VEGFR targeted therapy monitored with VEGFR1 and FSHR targeted microbubbles. Scientific reports 16 32355171
2019 Characterization of gonadotropin receptors Fshr and Lhr in Japanese medaka, Oryzias latipes. General and comparative endocrinology 16 31536722
2013 SMAD3 regulates the diverse functions of rat granulosa cells relating to the FSHR/PKA signaling pathway. Reproduction (Cambridge, England) 16 23690627
2013 FSHB-211 and FSHR 2039 are associated with serum levels of follicle-stimulating hormone and antimüllerian hormone in healthy girls: a longitudinal cohort study. Fertility and sterility 16 23850305
2020 FSHR ablation induces depression-like behaviors. Acta pharmacologica Sinica 15 32203083
2019 Tyrosine nitrations impaired intracellular trafficking of FSHR to the cell surface and FSH-induced Akt-FoxO3a signaling in human granulosa cells. Aging 15 31097679
2016 Contribution of polymorphisms in ESR1, ESR2, FSHR, CYP19A1, SHBG, and NRIP1 genes to migraine susceptibility in Turkish population. Journal of genetics 15 27019440
2015 Prostate cancer imaging of FSHR antagonist modified with a hydrophilic linker. Contrast media & molecular imaging 15 26286841
2012 Differential regulation of gonadotropin receptors (fshr and lhcgr) by epidermal growth factor (EGF) in the zebrafish ovary. General and comparative endocrinology 15 23036736
2021 Investigation of the FSHR, CYP11, and INSR Mutations and Polymorphisms in Iranian Infertile Women with Polycystic Ovary Syndrome (PCOS). Reports of biochemistry & molecular biology 14 33969141
2021 A major QTL at the LHCGR/FSHR locus for multiple birth in Holstein cattle. Genetics, selection, evolution : GSE 14 34217202
2019 Association of FSHR missense mutations with female infertility, in silico investigation of their molecular significance and exploration of possible treatments using virtual screening and molecular dynamics. Analytical biochemistry 14 31521670
2013 Gender-specific association between FSHR and PPARG common variants and human longevity. Rejuvenation research 14 22985084
2013 Fine-mapping an association of FSHR with preterm birth in a Finnish population. PloS one 14 24205076
2011 Up-regulation of FSHR expression during gonadal sex determination in the frog Rana rugosa. General and comparative endocrinology 14 21521644
2019 Tanshinone IIA attenuates estradiol-induced polycystic ovarian syndrome in mice by ameliorating FSHR expression in the ovary. Experimental and therapeutic medicine 13 30988730
2018 The Impact of FSHR Gene Polymorphisms Ala307Thr and Asn680Ser in the Endometriosis Development. DNA and cell biology 13 29683332
2014 Genotyping common FSHR polymorphisms based on competitive amplification of differentially melting amplicons (CADMA). Journal of assisted reproduction and genetics 13 25241129
2011 Follicle-stimulating hormone receptor (FSHR)-derived peptide vaccine induced infertility in mice without pathological effect on reproductive organs. Reproduction, fertility, and development 13 21557921
2006 Distal regulatory elements are required for Fshr expression, in vivo. Molecular and cellular endocrinology 13 17097219
2023 Paeoniflorin Alleviates Cisplatin-Induced Diminished Ovarian Reserve by Restoring the Function of Ovarian Granulosa Cells via Activating FSHR/cAMP/PKA/CREB Signaling Pathway. Molecules (Basel, Switzerland) 12 38138611
2017 The Common Follicle-Stimulating Hormone Receptor (FSHR) Promoter Polymorphism FSHR -29G > A Affects Androgen Production in Normal Human Small Antral Follicles. Frontiers in endocrinology 12 28626448
2017 Expression of FSHR in chondrocytes and the effect of FSH on chondrocytes. Biochemical and biophysical research communications 12 29133260
2009 A novel dominant B-cell epitope of FSHR identified by molecular docking induced specific immune response and suppressed fertility. Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 12 19906003
2021 Association of FSHR, LH, LHR, BMP15, GDF9, AMH, and AMHR polymorphisms with poor ovarian response in patients undergoing in vitro fertilization. JBRA assisted reproduction 11 33739800
2021 TRIB3 regulates FSHR expression in human granulosa cells under high levels of free fatty acids. Reproductive biology and endocrinology : RB&E 11 34503515
2018 Deletion of fetoplacental Fshr inhibits fetal vessel angiogenesis in the mouse placenta. Molecular and cellular endocrinology 11 29715497
2015 LH (Trp8Arg/Ile15Thr), LHR (insLQ) and FSHR (Asn680Ser) polymorphisms genotypic prevalence in women with endometriosis and infertility. Journal of assisted reproduction and genetics 11 25935136
2013 Immunohistochemical detection of follicle stimulating hormone receptor (FSHR) in neuroendocrine tumours. Endokrynologia Polska 11 24002953