FSHR

Gene Summary

Gene:FSHR; follicle stimulating hormone receptor
Aliases: LGR1, ODG1, FSHR1, FSHRO
Location:2p16.3
Summary:The protein encoded by this gene belongs to family 1 of G-protein coupled receptors. It is the receptor for follicle stimulating hormone and functions in gonad development. Mutations in this gene cause ovarian dysgenesis type 1, and also ovarian hyperstimulation syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Protein:follicle-stimulating hormone receptor
Source:NCBIAccessed: 01 September, 2019

Ontology:

What does this gene/protein do?
Show (17)
Pathways:What pathways are this gene/protein implicaed in?
Show (2)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 01 September 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Ovary
  • Testosterone
  • Puberty, Precocious
  • Testicular Cancer
  • Cervical Cancer
  • Ovarian Cancer
  • Uterine Cancer
  • Mutation
  • Asian Continental Ancestry Group
  • Follicle Stimulating Hormone
  • Messenger RNA
  • Chromosome 2
  • Risk Factors
  • Receptors, LH
  • Genotype
  • Adolescents
  • Ovulation Induction
  • Genetic Loci
  • Validation Studies as Topic
  • Childhood Cancer
  • European Continental Ancestry Group
  • Alleles
  • Polycystic Ovary Syndrome
  • Receptors, FSH
  • Genetic Predisposition
  • Polymorphism
  • Pregnancy
  • Single Nucleotide Polymorphism
  • Granulosa Cell Tumor
  • Cancer Gene Expression Regulation
  • Linkage Disequilibrium
  • Case-Control Studies
  • Cohort Studies
  • Singapore
  • Signal Transduction
  • Amino Acid Substitution
  • Base Sequence
  • China
  • Genetic Association Studies
  • Thyroid Cancer
  • Genome-Wide Association Study
Tag cloud generated 01 September, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (5)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: FSHR (cancer-related)

Branavan U, Muneeswaran K, Wijesundera S, et al.
Identification of selected genetic polymorphisms in polycystic ovary syndrome in Sri Lankan women using low cost genotyping techniques.
PLoS One. 2018; 13(12):e0209830 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Polycystic ovary syndrome (PCOS), the commonest endocrine disorder affecting young women, appears to be a multigenic trait with contributing genes being unclear. Hence, analysis of polymorphisms in multiple candidate genes is required. Currently available genotyping methods are expensive, time-consuming with limited analytical sensitivity.
AIM: (i) Develop and validate high resolution melting (HRM) assay and allele-specific real-time quantitative PCR (AS-qPCR) for genotyping selected SNPs associated with PCOS. (ii) Identify selected SNPs and their association with a Sri Lankan cohort of well-characterized PCOS.
METHODS: DNA was extracted from women with well-characterized PCOS from adolescence (n = 55) and ethnically matched controls (n = 110). FTO (Fat mass and obesity associated gene; rs9939609), FSHB (Follicle stimulating hormone beta subunit; rs6169), FSHR (Follicle stimulating hormone receptor; rs6165/rs6166), and INSR (Insulin receptor; rs1799817) genes were genotyped using HRM assay. GnRH1 (Gonadotropin releasing hormone; rs6185), LHB (Luteinizing hormone beta subunit; rs1800447/rs34349826) and LHCGR (Luteinizing hormone/choriogonadotropin receptor; rs2293275) genes were genotyped using AS-qPCR method. Genotyping results were validated using Sanger sequencing.
RESULTS: A significant association was observed within FTO gene polymorphism (rs9939609) and PCOS. Genotype frequency of FTO gene (rs9939609)-cases versus controls were TT-36.4% vs.65.4% (p<0.05), AT-23.6% vs.20.9%, AA-40% vs.13.6% (p<0.05). Genotype frequencies of the SNPs GnRH1 (rs6185), FSHB (rs6169), FSHR (rs6165 & rs6166), LHB (rs1800447 & rs34349826), LHCGR (rs2293275) and INSR (rs1799817) were not significantly different between cases and controls (p>0.05). Only the mutant alleles were observed for LHB rs1800447 and rs34349826 SNPs in both groups. The HRM and AS-qPCR assay results had 100% concordance with sequencing results.
CONCLUSIONS: FTO gene rs9939609 polymorphism is significantly more prevalent among Sri Lankan PCOS subjects while the other selected SNPs of HPG axis genes and INSR gene showed no association. HRM and AS-qPCR assays provide a reliable, fast and user-friendly genotyping method facilitating wider implication in clinical practice.

Pawlikowski Łódź M
Expression of follicle stimulating hormone receptors in intra-tumoral vasculature and in tumoral cells - the involvement in tumour progression and the perspectives of application in cancer diagnosis and therapy.
Endokrynol Pol. 2018; 69(2):192-198 [PubMed] Related Publications
In normal conditions follicle stimulating hormone receptors (FSHR) are expressed in zona granulosa cells of the ovary and Sertoli cells of the testis. However, the ectopic expression of FSHR was recently discovered in intra-tumoral blood vessels endothelia and/or in tumoral cells of many extra-gonadal human tumors (particularly in endocrine tumours). The paper reviews the data concerning the appearance of ectopic FSHR in particular human neoplasms. The possible involvement of FSHR in tumor progression and the use of FSHR examination for diagnostic purposes is also reviewed. Finally, the putative role of FSHR as a new target in oncological therapy is also discussed.

Zhang M, Zhang M, Wang J, et al.
Retro-inverso follicle-stimulating hormone peptide-mediated polyethylenimine complexes for targeted ovarian cancer gene therapy.
Drug Deliv. 2018; 25(1):995-1003 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: The development of nanoparticle drug delivery systems with targeted ligands has the potential to increase treatment efficiency in ovarian cancer.
METHODS: We developed a 21-amino acid peptide, YTRDLVYGDPARPGIQGTGTF (L-FP21) conjugated to polyethylenimine (PEI) and methoxy polyethylene glycol (mPEG) to prepare a nanoparticle drug vehicle to target follicle-stimulating hormone receptor (FSHR) in ovarian cancer. At the same time, we optimized the ligand of the nanoparticle vehicle using D-peptides, which consist of D-amino acids (D-FP21). Nanoparticle vehicles carrying the therapeutic gene plasmid growth-regulated oncogene alpha (pGRO-α) short hairpin RNA (shRNA) (FP21-PEG-PEI/pGRO-α) were prepared for further investigation.
RESULTS: Compared with L-FP21, D-FP21 exhibited improved biological stability and higher uptake rate for FSHR-expressing ovarian cancer cells. The cytotoxicity of the L, D-FP21-PEG-PEI/pGRO-α complexes were significantly lower than that of the PEI/pGRO-α complex. The nanoparticle drug with the targeted ligand showed higher transfection efficiencies and improved anti-proliferation effects for ovarian cancer cells than that without the targeted ligand (mPEG-PEI/pGRO-α). Furthermore, an in vivo evaluation of an antitumor assay indicated that D-FP21-PEG-PEI/pGRO-α inhibited the growth of tumor spheroids considerably more than L-FP21-PEG-PEI/pGRO-α; their tumor inhibition rates were 58.5% and 33.3%, respectively.
CONCLUSIONS: D-FP21-PEG-PEI/plasmid DNA is a safe and efficient gene delivery vehicle for ovarian cancer targeted therapy.

Zhu K, Li S, Liu J, et al.
Role of RAB5A in FSHR-mediated signal transduction in human granulosa cells.
Reproduction. 2018; 155(6):505-514 [PubMed] Related Publications
Polycystic ovary syndrome, a common condition characterized by endocrine dysfunction, menstrual irregularity, anovulation and polycystic ovaries, affects 5-7% of reproductive-age women.

Hong SS, Zhang MX, Zhang M, et al.
Follicle-stimulating hormone peptide-conjugated nanoparticles for targeted shRNA delivery lead to effective gro-α silencing and antitumor activity against ovarian cancer.
Drug Deliv. 2018; 25(1):576-584 [PubMed] Free Access to Full Article Related Publications
The distinct hormone molecules and receptors, such as follicle-stimulating hormone receptor (FSHR) in ovarian cancer, provide opportunities for more precisely targeted therapy. We previously developed FSHR-mediated nanoparticles and found that FSH peptides on the surface of nanoparticles improved the delivery of short interfering RNA (siRNA) into ovarian cancer cells. However, the high toxicity of the nanoparticles and the transient silencing of the siRNA in vivo limited further study. Here, we developed FSH peptide-conjugated nanoparticles with an increased amount of polyethylene glycol (PEG) grafting and encapsulated short hairpin RNA (shRNA) to silence the target gene, growth-regulated oncogene α (gro-α). The nanoparticle complexes exhibited good stability over three weeks. Expression of the target gene, gro-α, was significantly down-regulated by gro-α shRNA-loaded nanoparticles conjugated with FSH peptides (FSH33-G-NP) in FSHR-positive HEY cells. Cell proliferation, migration, and invasion were also inhibited by FSH33-G-NP. Tumor growth was delayed significantly in the mice treated with FSH33-G-NP. No significant loss of body weight or severe toxic effects were observed in any groups. In conclusion, gro-α shRNA-loaded nanoparticles conjugated with FSH peptides overcame the drawbacks of the in vivo application of RNAi therapeutics and polymer-based nanocarriers and showed safe antitumor efficacy. Our study might contribute to the application of FSHR-based targeted therapy and imaging in cancer.

Schack LMH, Petersen SE, Nielsen S, et al.
Validation of genetic predictors of late radiation-induced morbidity in prostate cancer patients.
Acta Oncol. 2017; 56(11):1514-1521 [PubMed] Related Publications
INTRODUCTION: Normal tissue morbidity sets the dose limit for radiotherapy (RT) in cancer treatment and has importance for quality of life for cancer survivors. A previous study of prostate cancer patients treated with RT generated clinical data for radiation-induced morbidity measured by anorectal physiological methods and validated questionnaires. Other studies have identified genetic predictors associated with late radiation-induced morbidity outcome. We have expanded biobank material aiming to validate single nucleotide polymorphisms (SNPs) and a gene expression classifier with endpoints on patient-reported outcomes and biomechanical properties of the anorectum from our cohort matching originally published endpoints.
MATERIALS AND METHODS: The present cohort of prostate cancer patients was treated with RT curative intent in 1999-2007. Nine SNPs associated with late radiation-induced morbidity were tested in 96 patients (rs2788612, rs1800629, rs264663, rs2682585, rs2268363, rs1801516, rs13035033, rs7120482 and rs17779457). A validated gene expression profile predictive of resistance to radiation-induced skin fibrosis was tested in 42 patients. An RT-induced anorectal dysfunction score (RT-ARD) served as a fibrosis-surrogate and a measure of overall radiation-induced morbidity.
RESULTS: The lowest p-value found in the genotype analyses was for SNP rs2682585 minor allele (A) in the FSHR gene and the RT-ARD score with odds ratios (OR) = 1.76; 95% CI (0.98-3.17) p = .06, which was out of concordance with original data showing a protective effect of the minor allele. The gene expression profile in patients classified as fibrosis-resistant was associated with high RT-ARD scores OR 4.18; 95% CI (1.1-16.6), p = .04 conflicting with the hypothesis that fibrosis-resistant patients would experience lower RT-ARD scores.
CONCLUSIONS: We aimed to validate nine SNPs and a gene expression classifier in a cohort of prostate cancer patients with unique scoring of radiation-induced morbidity. One significant association was found, pointing to the opposite direction of originally published data. We conclude that the material was not able to validate previously published genetic predictors of radiation-induced morbidity.

Xuan Q, Zhong X, Li W, et al.
CtBP2 is associated with angiogenesis and regulates the apoptosis of prostate cancer cells.
Oncol Rep. 2017; 38(2):1259-1267 [PubMed] Related Publications
Angiogenesis is associated with prostate cancer (PCa) development and progression. Aberrant expression of C-terminal binding protein (CtBP)2 has been observed in PCa, but whether its change in expression plays a significant role in angiogenesis has not been completely characterized. we attempted to integrate and analyze the genome-wide association study (GWAS) of follicle stimulating hormone receptor (FSHR) and CtBP2, the Cancer Genome Atlas (TCGA) data and CtBP2 binding data in CistromeMap (18) to explore the mechanism of CtBP2 in PCa, and performed pathway enrichment analysis. We revealed that the top 6 pathways were closely related with angiogenesis. We used siRNA and overexpression plasmids to silence and overexpress CtBP2 expression. Altered expression of CtBP2 affected the expression of VEGFA, FSHR, FHL2 and SMAD3 which are closely related with angiogenesis. In addition, silencing of CtBP2 markedly increased the apoptosis of PCa cells in vitro, and decreased the expression of IL-8, AT2R, CCND1 and MMP9 which are associated with cancer progression. These results highlight the association between CtBP2 and angiogenesis in PCa and indicate that CtBP2 may be a potential therapeutic target for PCa.

Kim JJ, Choi YM, Hong MA, et al.
FSH receptor gene p. Thr307Ala and p. Asn680Ser polymorphisms are associated with the risk of polycystic ovary syndrome.
J Assist Reprod Genet. 2017; 34(8):1087-1093 [PubMed] Free Access to Full Article Related Publications
PURPOSE: The purpose of this study was to investigate whether the follicle-stimulating hormone receptor (FSHR) gene p. Thr307Ala (c.919A>G, rs6165) and p. Asn680Ser (c.2039A>G, rs6166) polymorphisms are associated with susceptibility to polycystic ovary syndrome (PCOS).
METHODS: Genotyping was performed in 377 women with PCOS and 388 age-matched controls. Difference in the genotype distribution was assessed using a Fisher's exact or chi-square test, and continuous variables were compared using a Student's t test. To evaluate the association between the presence of PCOS status and SNP, logistic regression analyses were performed.
RESULTS: Linkage disequilibrium between the two polymorphisms was approximately complete (r
CONCLUSIONS: Findings of this study suggest a significant association between FSHR gene p. Thr307Ala or p. Asn680Ser coding sequence change and PCOS. The variant homozygote genotype results in a higher risk of PCOS.

Colombe S, Houllier L, Fleurot E, et al.
Syndecan 1 represses cell growth and FSH responsiveness in human granulosa cells.
Reproduction. 2017; 153(6):797-808 [PubMed] Related Publications
Albeit devoid of intrinsic catalytic activity, the transmembrane heparan sulphate proteoglycan syndecan 1 plays critical roles in cellular processes such as extracellular matrix crosstalk, cytoskeletal organization, cell spreading, proliferation and differentiation. During the ovarian cycle, the expression of syndecan 1 in granulosa cells shows cyclic variation suggesting that it might fulfil specific roles in follicle development. To investigate its physiological roles on granulosa cells, syndecan 1 was overexpressed in human granulosa cell line KGN which retains features of granulosa cells from small antral follicle such as estradiol (E2) synthesis and low expression of functional FSH receptor (FSHR). We demonstrated that overexpression of syndecan 1 in immature granulosa cells (KGN-SDC1) induces a profound alteration in their intrinsic characteristics including enhanced spreading and attachment, both associated with a reduced growth rate. Flow cytometry analysis revealed that syndecan 1 overexpression increases the percentage of KGN cells in quiescent phase. This partial cell cycle exit is concordant with downregulated levels of

Zidi S, Stayoussef M, Alsaleh BL, et al.
Effect of Follicle Stimulating Hormone Receptor Gene Polymorphisms in Cervical Cancer Risk.
Pathol Oncol Res. 2017; 23(3):565-572 [PubMed] Related Publications
For the first time in the word, we investigated the association between five FSHR polymorphisms with the risk of cervical cancer among Tunisians. Study subjects comprised 112 Cervical Cancer (CC) patients and 164 control women. Genotyping of FSHR rs6166, rs1007541, rs11692782, rs2055571 and rs1394205 variants was done by realtime PCR, with defined clusters. The allelic distributions of the tested FSHR SNPs were comparable between CC patients and control women. In contrast, the heterozygous genotype of rs1007541 was associated with 1.8-fold increased risk of CC. Stratification according to FIGO staging revealed that the minor allele of rs1007541 was more frequent among advanced tumor stage patients, with 11-fold increased risk of CC [P < 0.0001; OR (95 % CI) = 11.32 (7.46-17.18)]. However, no significant allelic association was revealed in the rest of analyzed FSHR SNPs. Haploview analysis showed high Linkage disequilibrium (LD) between rs2055571 and rs1394205. Haplotype analysis revealed a lack of association between cases and controls. However, analysis of CC patient subgroups demonstrated enrichment of GGTAG haplotype in early tumor stage [P = 0.025; OR (95 % CI) = 0.07 (0.01-0.70)]. The FSHR variants and haplotypes may be a genetic markers for CC susceptibility and evolution among Tunisian women.

Perales-Puchalt A, Svoronos N, Rutkowski MR, et al.
Follicle-Stimulating Hormone Receptor Is Expressed by Most Ovarian Cancer Subtypes and Is a Safe and Effective Immunotherapeutic Target.
Clin Cancer Res. 2017; 23(2):441-453 [PubMed] Free Access to Full Article Related Publications
PURPOSE: To define the safety and effectiveness of T cells redirected against follicle-stimulating hormone receptor (FSHR)-expressing ovarian cancer cells.
EXPERIMENTAL DESIGN: FSHR expression was determined by Western blotting, immunohistochemistry, and qPCR in 77 human ovarian cancer specimens from 6 different histologic subtypes and 20 human healthy tissues. The effectiveness of human T cells targeted with full-length FSH in vivo was determined against a panel of patient-derived xenografts. Safety and effectiveness were confirmed in immunocompetent tumor-bearing mice, using constructs targeting murine FSHR and syngeneic T cells.
RESULTS: FSHR is expressed in gynecologic malignancies of different histologic types but not in nonovarian healthy tissues. Accordingly, T cells expressing full-length FSHR-redirected chimeric receptors mediate significant therapeutic effects (including tumor rejection) against a panel of patient-derived tumors in vivo In immunocompetent mice growing syngeneic, orthotopic, and aggressive ovarian tumors, fully murine FSHR-targeted T cells also increased survival without any measurable toxicity. Notably, chimeric receptors enhanced the ability of endogenous tumor-reactive T cells to abrogate malignant progression upon adoptive transfer into naïve recipients subsequently challenged with the same tumor. Interestingly, FSHR-targeted T cells persisted as memory lymphocytes without noticeable PD-1-dependent exhaustion during end-stage disease, in the absence of tumor cell immunoediting. However, exosomes in advanced tumor ascites diverted the effector activity of this and other chimeric receptor-transduced T cells away from targeted tumor cells.
CONCLUSIONS: T cells redirected against FSHR

Papadimitriou K, Kountourakis P, Kottorou AE, et al.
Follicle-Stimulating Hormone Receptor (FSHR): A Promising Tool in Oncology?
Mol Diagn Ther. 2016; 20(6):523-530 [PubMed] Related Publications
The cellular pathway of follicle-stimulating hormone (FSH) and its receptor (FSHR) is typically involved in reproduction in mammals. In humans, the FSHR is normally found in cells of the testis and the ovary, while it is scarcely expressed in other normal tissues. The expression of FSH/FSHR is studied in prostate, thyroid, and ovarian cancer tissues. Recently, the expression of FSHR was uniformly documented in malignant vascular endothelial cells from different tumor types, while in normal or inflammatory tissues its expression was scarce, suggesting a potential role of a pan-receptor in cancer. Subsequent studies have attempted to verify this unique specificity of this molecule and further define its features in malignant microenvironments but have had conflicting results, mostly because of differing techniques and immaturity of antibodies. Still, the lack of FSHR expression in most non-cancerous cells, in contrast to its specific correlation with the malignant tissue microenvironment, implies a potential role as both a diagnostic and a therapeutic tool. FSHR might also have a very specific role in malignancies, such as angiogenic and/or growth factor malignancies, but this is yet to be validated. Moreover, the expression of FSHR in endothelial malignant cells could have a predictive impact on disease progression, especially in relation to therapies targeting the tumor vasculature. In this review we look deep into the physiology of the FSH/FSHR pathway and evaluate the potential of FSHR as a predictive and prognostic tool in oncology.

Jones MR, Goodarzi MO
Genetic determinants of polycystic ovary syndrome: progress and future directions.
Fertil Steril. 2016; 106(1):25-32 [PubMed] Related Publications
The field of the genetics of polycystic ovary syndrome (PCOS) has relatively recently moved into the era of genome-wide association studies. This has led to the discovery of 16 robust loci for PCOS. Some loci contain genes with clear roles in reproductive (LHCGR, FSHR, and FSHB) and metabolic (INSR and HMGA2) dysfunction in the syndrome. The next challenge facing the field is the identification of causal variants and genes and the role they play in PCOS pathophysiology. The potential for gene discovery to improve diagnosis and treatment of PCOS is promising, though there is much to be done in the field before the current findings can be translated to the clinic.

Feng Z, Wen H, Bi R, et al.
A clinically applicable molecular classification for high-grade serous ovarian cancer based on hormone receptor expression.
Sci Rep. 2016; 6:25408 [PubMed] Free Access to Full Article Related Publications
To establish an effective hormone receptor-based molecular classification of high-grade serous ovarian cancer (HGSC), we retrospectively examined 875 consecutive HGSC patients who underwent primary surgery at our hospital and constructed tissue microarrays from these specimens. The expression levels of the hormone receptors were as follows: ER 64.4%, PR 12.6%, AR 35.6%, FSHR 54.5%, LHR 34.8%, and GnRHR 88.3%. Based on clustering of their expression patterns, we classified patients into five subgroups with distinctive clinical features (PR+, PR - ER + AR+, PR - ER + AR-, PR - ER - AR+, and PR - ER - AR-). Patients in the PR + group were younger compared to those in the other groups (p < 0.001). More patients were of advanced stage in the PR - ER + AR- group than the other groups (p = 0.020). A greater proportion of patients were sensitive to platinum-based chemotherapy in the PR - ER - AR + group compared with the other groups (p = 0.034). A trend of increasing risk of death was observed among these subgroups (p < 0.001). In the multivariate analysis, patients also had orderly increased hazard ratios for death in the PR + (HR = 2.256, 95% CI, 0.983-5.175), PR - ER + AR + (HR = 2.188, 95% CI, 1.004-4.796), PR - ER - AR- (HR = 2.316, 95% CI, 1.097-5.082) and PR - ER + AR- (HR = 2.928, 95% CI, 1.366-6.276) subgroups compared to the PR - ER - AR+ subgroup. Our classification could help predict patient clinical outcomes, guide individual treatments and stratify patients in future clinical trials.

Artimani T, Saidijam M, Aflatoonian R, et al.
Downregulation of adiponectin system in granulosa cells and low levels of HMW adiponectin in PCOS.
J Assist Reprod Genet. 2016; 33(1):101-10 [PubMed] Free Access to Full Article Related Publications
PURPOSE: The purpose of the study was to investigate changes in adiponectin system expression in granulosa cells (GCs) and high molecular weight adiponectin levels in serum and follicular fluid (FF) of 40 women with polycystic ovary syndrome (PCOS) compared to those in 40 women with normal ovary function.
METHODS: Adiponectin (Adipo), adiponectin receptor 1 (AdipoR1), and adiponectin receptor 2 (AdipoR2) messenger RNA (mRNA) expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). High molecular weight (HMW) adiponectin protein concentration was evaluated by ELISA method. Data were analyzed using Student's t test and one-way ANOVA in SPSS 21 software. At oocyte retrieval, FF was aspirated and GCs were obtained from a pooled collection of FF per each patient.
RESULTS: PCR results showed expression of adiponectin, AdipoR1, AdipoR2, follicle-stimulating hormone receptor (FSHR), and luteinizing hormone receptor (LHR) in GCs. After controlling body mass index (BMI) values, qRT-PCR demonstrated a decreased expression of adiponectin system in GCs of PCOS patients compared to those in controls (p = 0.001). There was a strong positive correlation among AdipoR1 and AdipoR2 expression and also among FSH and LH receptor expression. (Both r = 0.8, p = 0.001). There were low levels of high molecular weight adiponectin in the serum of PCOS patients with controlled ovarian hyperstimulation (30.19 ± 4.3 ng/ml) compared to the controls (48.47 ± 5.9 ng/ml) and in the FF of PCOS patients with controlled ovarian hyperstimulation (7.86 ± 1.44 ng/ml) compared to the controls (14.22 ± 2.01 ng/ml; p = 0.02).
CONCLUSIONS: Lower expression of adiponectin and its receptors in GCs might be an important manifestation in gonadotropin-stimulated PCOS patients which could influence the physiologic adiponectin roles such as interaction with insulin and LH in induction of GC gene expression.

Liu Y, Yen HY, Austria T, et al.
A Mouse Model That Reproduces the Developmental Pathways and Site Specificity of the Cancers Associated With the Human BRCA1 Mutation Carrier State.
EBioMedicine. 2015; 2(10):1318-30 [PubMed] Free Access to Full Article Related Publications
Predisposition to breast and extrauterine Müllerian carcinomas in BRCA1 mutation carriers is due to a combination of cell-autonomous consequences of BRCA1 inactivation on cell cycle homeostasis superimposed on cell-nonautonomous hormonal factors magnified by the effects of BRCA1 mutations on hormonal changes associated with the menstrual cycle. We used the Müllerian inhibiting substance type 2 receptor (Mis2r) promoter and a truncated form of the Follicle stimulating hormone receptor (Fshr) promoter to introduce conditional knockouts of Brca1 and p53 not only in mouse mammary and Müllerian epithelia, but also in organs that control the estrous cycle. Sixty percent of the double mutant mice developed invasive Müllerian and mammary carcinomas. Mice carrying heterozygous mutations in Brca1 and p53 also developed invasive tumors, albeit at a lesser (30%) rate, in which the wild type alleles were no longer present due to loss of heterozygosity. While mice carrying heterozygous mutations in both genes developed mammary tumors, none of the mice carrying only a heterozygous p53 mutation developed such tumors (P < 0.0001), attesting to a role for Brca1 mutations in tumor development. This mouse model is attractive to investigate cell-nonautonomous mechanisms associated with cancer predisposition in BRCA1 mutation carriers and to investigate the merit of chemo-preventive drugs targeting such mechanisms.

Du T, Duan Y, Li K, et al.
Statistical Genomic Approach Identifies Association between FSHR Polymorphisms and Polycystic Ovary Morphology in Women with Polycystic Ovary Syndrome.
Biomed Res Int. 2015; 2015:483726 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the follicle stimulating hormone receptor (FSHR) gene are associated with PCOS. However, their relationship to the polycystic ovary (PCO) morphology remains unknown. This study aimed to investigate whether PCOS related SNPs in the FSHR gene are associated with PCO in women with PCOS.
METHODS: Patients were grouped into PCO (n = 384) and non-PCO (n = 63) groups. Genomic genotypes were profiled using Affymetrix human genome SNP chip 6. Two polymorphisms (rs2268361 and rs2349415) of FSHR were analyzed using a statistical approach.
RESULTS: Significant differences were found in the allele distributions of the GG genotype of rs2268361 between the PCO and non-PCO groups (27.6% GG, 53.4% GA, and 19.0% AA versus 33.3% GG, 36.5% GA, and 30.2% AA), while no significant differences were found in the allele distributions of the GG genotype of rs2349415. When rs2268361 was considered, there were statistically significant differences of serum follicle stimulating hormone, estradiol, and sex hormone binding globulin between genotypes in the PCO group. In case of the rs2349415 SNP, only serum sex hormone binding globulin was statistically different between genotypes in the PCO group.
CONCLUSIONS: Functional variants in FSHR gene may contribute to PCO susceptibility in women with PCOS.

Zhao S, Tian Y, Gao X, et al.
Family-based analysis of eight susceptibility loci in polycystic ovary syndrome.
Sci Rep. 2015; 5:12619 [PubMed] Free Access to Full Article Related Publications
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that is proposed to have a genetic basis. A recent genome-wide association study (GWAS) identified eight new risk loci that are independently associated with PCOS. To further validate the findings, a total of 321 case-parent trios (963 participants) who had a proband affected with PCOS were recruited for the family-based study. The transmission disequilibrium test (TDT) was used to analyze associations between PCOS and ten single nucleotide polymorphisms (SNPs) mapped to eight new susceptibility loci. Significant differences in transmission were observed for the SNPs rs2349415 (located in the FSHR gene, P = 0.0001) and rs3802457 (located in the C9orf3 gene, P = 0.0001), even after correction for multiple testing bias. The present data provides further evidence for an association between two susceptibility loci, 2p16.3 and 9q22.32, and PCOS. Follow-up functional studies on the FSHR and C9orf3 genes are required to understand their roles in PCOS development.

Urbanska K, Stashwick C, Poussin M, Powell DJ
Follicle-Stimulating Hormone Receptor as a Target in the Redirected T-cell Therapy for Cancer.
Cancer Immunol Res. 2015; 3(10):1130-7 [PubMed] Free Access to Full Article Related Publications
Adoptive transfer of T cells engineered to express chimeric immunoreceptors is an effective strategy to treat hematologic cancers; however, the use of this type of therapy for solid cancers, such as ovarian cancer, remains challenging because a safe and effective immunotherapeutic target has not yet been identified. Here, we constructed and evaluated a novel redirected T-cell-based immunotherapy targeting human follicle-stimulating hormone receptor (FSHR), a highly conserved molecule in vertebrate animals with expression limited to gonadal tissues, ovarian cancer, and cancer-associated vasculature. Receptor ligand-based anti-FSHR immunoreceptors were constructed that contained small binding fragments from the ligand for FSHR, FSH, fused to T-cell transmembrane and T-cell signaling domains. Human T cells transduced to express anti-FSHR immunoreceptors were specifically immunoreactive against FSHR-expressing human and mouse ovarian cancer cell lines in an MHC-nonrestricted manner and mediated effective lysis of FHSR-expressing tumor cells, but not FSHR-deficient targets, in vitro. Similarly, the outgrowth of human ovarian cancer xenografts in immunodeficient mice was significantly inhibited by the adoptive transfer of FSHR-redirected T cells. Our experimental observations show that FSHR is a promising immunotherapeutic target for ovarian cancer and support further exploration of FSHR-targeted immune therapy approaches for patients with cancer.

Liu Z, Ren YA, Pangas SA, et al.
FOXO1/3 and PTEN Depletion in Granulosa Cells Promotes Ovarian Granulosa Cell Tumor Development.
Mol Endocrinol. 2015; 29(7):1006-24 [PubMed] Free Access to Full Article Related Publications
The forkhead box (FOX), FOXO1 and FOXO3, transcription factors regulate multiple functions in mammalian cells. Selective inactivation of the Foxo1 and Foxo3 genes in murine ovarian granulosa cells severely impairs follicular development and apoptosis causing infertility, and as shown here, granulosa cell tumor (GCT) formation. Coordinate depletion of the tumor suppressor Pten gene in the Foxo1/3 strain enhanced the penetrance and onset of GCT formation. Immunostaining and Western blot analyses confirmed FOXO1 and phosphatase and tensin homolog (PTEN) depletion, maintenance of globin transcription factor (GATA) 4 and nuclear localization of FOXL2 and phosphorylated small mothers against decapentaplegic (SMAD) 2/3 in the tumor cells, recapitulating results we observed in human adult GCTs. Microarray and quantitative PCR analyses of mouse GCTs further confirmed expression of specific genes (Foxl2, Gata4, and Wnt4) controlling granulosa cell fate specification and proliferation, whereas others (Emx2, Nr0b1, Rspo1, and Wt1) were suppressed. Key genes (Amh, Bmp2, and Fshr) controlling follicle growth, apoptosis, and differentiation were also suppressed. Inhbb and Grem1 were selectively elevated, whereas reduction of Inha provided additional evidence that activin signaling and small mothers against decapentaplegic (SMAD) 2/3 phosphorylation impact GCT formation. Unexpectedly, markers of Sertoli/epithelial cells (SRY [sex determining region Y]-box 9/keratin 8) and alternatively activated macrophages (chitinase 3-like 3) were elevated in discrete subpopulations within the mouse GCTs, indicating that Foxo1/3/Pten depletion not only leads to GCTs but also to altered granulosa cell fate decisions and immune responses. Thus, analyses of the Foxo1/3/Pten mouse GCTs and human adult GCTs provide strong evidence that impaired functions of the FOXO1/3/PTEN pathways lead to dramatic changes in the molecular program within granulosa cells, chronic activin signaling in the presence of FOXL2 and GATA4, and tumor formation.

Saxena R, Georgopoulos NA, Braaten TJ, et al.
Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance.
Hum Reprod. 2015; 30(6):1454-9 [PubMed] Free Access to Full Article Related Publications
STUDY QUESTION: Are PCOS risk variants identified in women of Han Chinese ethnicity also associated with risk of PCOS or the phenotypic features of PCOS in European women?
SUMMARY ANSWER: One variant, rs2268361-T, in the intron of FSHR was associated with PCOS and lower FSH levels, while another variant rs705702-G near the RAB5B and SUOX genes was associated with insulin and glucose levels after oral glucose testing in women with PCOS of European ethnicity.
WHAT IS KNOWN ALREADY: Three of the eleven variants associated with PCOS in the Han Chinese genome-wide association studies were also associated with PCOS in at least one European population when corrected for multiple testing (DENND1A, THADA and YAP1). However, additional replication is needed to establish the importance of these variants in European women and to determine the relationship to PCOS phenotypic traits.
STUDY DESIGN, SIZE, DURATION: The study was a case-control examination in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston (Boston 1). Replication was performed in women from Greece (cases n = 884 and controls n = 311) and an additional cohort from Boston (Boston electronic medical record (EMR); n = 350 cases and n = 1258 controls).
PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Women had PCOS defined by the National Institutes of Health criteria in Boston 1 and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. The second cohort from Boston was defined using the EMR and natural language processing. Allele frequencies for variants associated with PCOS in Han Chinese women were examined in PCOS cases and controls, along with the relationship to quantitative traits.
MAIN RESULTS AND THE ROLE OF CHANCE: A variant rs2268361-T in an intron of FSHR was associated with PCOS (0.84 [0.76-0.93], OR [95% CI]; P = 0.002). The rs2268361-T was associated with lower FSH levels (-0.15 ± 0.05; P = 0.0029). A variant rs705702-G near RAB5B and SUOX was associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test.
LIMITATIONS, REASONS FOR CAUTION: The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS.
WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations.
STUDY FUNDING/COMPETING INTERESTS: The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals.
TRIAL REGISTRATION NUMBER: NCT00166569.

Qiu L, Liu J, Hei QM
Association between two polymorphisms of follicle stimulating hormone receptor gene and susceptibility to polycystic ovary syndrome: a meta-analysis.
Chin Med Sci J. 2015; 30(1):44-50 [PubMed] Related Publications
OBJECTIVE: To investigate the association between two polymorphisms of follicle stimulating hormone receptor (FSHR) gene and polycystic ovary syndrome (PCOS) susceptibility.
METHODS: Case-control studies on relationship of Thr307Ala and Asn680Ser polymorphisms in FSHR gene and PCOS susceptibility were searched from PubMed, ISI web of knowledge, EBSCO, and China National Knowledge Infrastructure (CNKI) databases up to March 21, 2013. The pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using fixed- or random-effect model based on heterogeneity test in 5 genotype models analyses.
RESULTS: A total of 11 studies were included in the Meta-analysis. The random-effect analysis showed Asn680Ser was significantly associated with the reduced susceptibility to PCOS with dominant model (Asn/Asn+Asn/Ser vs. Ser/Ser, OR=0.83, 95% CI: 0.69-1.00), recessive model (Asn/Asn vs. Asn/Ser+ Ser/Ser, OR=0.84, 95% CI: 0.72-0.98), homozygote comparison (Asn/Asn vs. Ser/Ser, OR=0.79, 95% CI: 0.63-0.98), and the allele contrast (Asn vs. Ser, OR=0.87, 95% CI: 0.79-0.97) respectively(P=0.02, I(2)=56.0%), being protective factors for PCOS. However, no significant associations were found between Thr307Ala and PCOS.
CONCLUSION: There might be a significant association between Asn680Ser polymorphism and PCOS.

Zhang Y, Luo Q, Wang N, et al.
LRG1 suppresses the migration and invasion of hepatocellular carcinoma cells.
Med Oncol. 2015; 32(5):146 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is a malignant tumor driven by complex pathological mechanisms and is characterized by fast progression and poor prognosis. The main cause of death in HCC patients is tumor metastasis. However, underlying molecular mechanisms of metastasis are largely unknown in HCC. In the present study, a novel metastasis-related gene, leucine-rich-alpha-2-glycoprotein 1 (LRG1), was identified in HCC. We revealed that LRG1 expression was downregulated in HCC tissues by quantitative real-time PCR and immunohistochemical staining. In vitro assays demonstrated LRG1 had no effect on cell proliferation. Migratory and invasive potential of HCC cells was reduced by ectopic overexpression of LRG1, whereas silencing LRG1 could enhance migration and invasion of HCC cells. Furthermore, exogenous recombinant human protein of LRG1 could inhibit migration and invasion of HCC cells in vitro. The above findings indicate that LGR1 is involved in the inhibition of HCC metastasis and it may function as a novel metastasis suppressor in HCC.

Planeix F, Siraj MA, Bidard FC, et al.
Endothelial follicle-stimulating hormone receptor expression in invasive breast cancer and vascular remodeling at tumor periphery.
J Exp Clin Cancer Res. 2015; 34:12 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Follicle-stimulating hormone receptor (FSHR) is expressed on the endothelial surface of blood vessels associated with solid tumor periphery, where angiogenesis is known to occur. The correlation between FSHR expression and formation of new peritumoral vessels has not been previously investigated.
METHODS: We used immunohistochemical techniques involving specific antibodies to detect FSHR and the endothelial markers (CD34, VEGFR2, and D2-40) in tissue samples from 83 patients with lymph node-negative, invasive breast cancer representing four main clinical treatment groups: HR+/HER2-, HR+/HER2+, HR-/HER2+ and triple-negative.
RESULTS: The FSHR+ vessels were exclusively located at breast cancer periphery, in a layer that extended 2 mm into and 5 mm outside of the tumor. The percentage of blood vessels expressing FSHR reached a maximum of 100% at the demarcation line between the tumor and the normal tissue. Common among FSHR+ vessels, regardless of breast cancer type, were the high densities of arterioles and venules (6.4 ± 1.4 and 13.9 ± 2.1 vessels/mm(2), respectively). These values were 3-fold higher that those noticed for CD34+ arterioles and venules associated with normal breast tissue located at a distance greater than 10 mm outside the tumors. The average density of FSHR+ and CD34+ blood vessels as well as of D2-40+ lymphatic vessels did not differ significantly among breast cancer subgroups. FSHR+ vessels did not express VEGFR2. The endothelial FSHR expression correlated significantly with the peritumoral CD34+ vessels' density (p < 0.001) and tumor size (p = 0.01).
CONCLUSION: Endothelial FSHR expression in breast cancer is associated with vascular remodeling at tumor periphery.

Almawi WY, Hubail B, Arekat DZ, et al.
Leutinizing hormone/choriogonadotropin receptor and follicle stimulating hormone receptor gene variants in polycystic ovary syndrome.
J Assist Reprod Genet. 2015; 32(4):607-14 [PubMed] Free Access to Full Article Related Publications
PURPOSE: Previous studies identified follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) genes as polycystic ovary syndrome (PCOS) susceptibility loci, which was dependent on the racial/ethnic background of studied population. We investigated the association of genetic variants in FSHR and LHCGR with PCOS in Bahraini Arab women.
METHODS: A retrospective case-control study, involving 203 women with PCOS, and 211 age- and ethnically-matched control women. FSHR and LHCGR genotyping was done by allelic exclusion method (real-time PCR).
RESULTS: Significantly lower frequencies of heterozygous LHCGR rs7371084 and FSHR rs11692782 genotype carriers were seen between women with PCOS vs. controls, and increased frequency of heterozygous homozygous LHCGR rs4953616 genotype carriers were detected between women with PCOS compared to control women. Limited linkage disequilibrium was noted among LHCGR and FSHR SNPs, and 2 blocks were constructed: the first (Block 1) spanning 61 kb contained the six tested LHCGR SNPs, and the second (Block 2) spanning 298 kb contained four of the five tested FSHR SNPs. Higher frequency of LHCGR GTCAAG haplotype was seen in women with PCOS compared to controls; the frequencies of the remaining LHCGR haplotypes, and all FSHR haplotypes were similar between cases and controls.
CONCLUSION: This is the first study to confirm the association of novel LHCGR (rs7371084, rs4953616) and FSHR (rs11692782) SNPs with PCOS. The differential association of LHCGR and FSHR variants with PCOS confirms the racial/ethnic contribution to their association with PCOS.

McAllister JM, Legro RS, Modi BP, Strauss JF
Functional genomics of PCOS: from GWAS to molecular mechanisms.
Trends Endocrinol Metab. 2015; 26(3):118-24 [PubMed] Free Access to Full Article Related Publications
Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.

Wu X, Zhu J, Zhao A
Ovarian hyperstimulation syndrome in a spontaneous pregnancy with invasive mole.
J Obstet Gynaecol Res. 2015; 41(5):817-22 [PubMed] Related Publications
Spontaneous ovarian hyperstimulation syndrome (sOHSS) is an extremely rare event. Herein, we report a case of severe sOHSS with invasive mole in a 29-year-old woman. In this case the full-blown OHSS developed after evacuation when the serum β-hCG value was declining. Also noticeable was a very high level of cancer antigen-125. Molecular biology study of the follicle-stimulating hormone (FSHR) gene did not detect exonic mutations, but revealed the presence of c.-29G>A (rs1394205) in the 5'-non-coding region of exon 1. The A307T and S680N polymorphisms of exon 10 of FSHR was Thr307 Asn680. Although sOHSS is a rare entity, clinicians must bear the differential diagnosis of sOHSS in mind if a patient presents with gross ascites and other symptoms of ovarian cancer, which also may be signs of OHSS. Whether the single nucleotide polymorphism rs1394205 affects the level of transcriptional activity of the FSHR gene needs to be studied in the future.

King TF, Conway GS
Swyer syndrome.
Curr Opin Endocrinol Diabetes Obes. 2014; 21(6):504-10 [PubMed] Related Publications
PURPOSE OF REVIEW: This review focuses on the pathogenesis, diagnosis, management and long-term outcomes of disorders of sex development, specifically women with Swyer syndrome (46,XY complete gonadal dysgenesis).
RECENT FINDINGS: Recent discoveries have broadened our understanding of the complex pathways involved in normal and abnormal sex development. In 46,XY gonadal dysgenesis, lack of testis development may be triggered by sex determining region Y, NR5A1, DHH or testis-determining gene loss-of-function mutations, DAX1 or WNT4 duplication or MAP3K1 gain-of-function mutations. The diagnosis and management of patients with Swyer syndrome is complex, and optimal care requires an experienced multidisciplinary team. Early diagnosis is vital because of the significant risk of germ cell tumour, and bilateral gonadectomy should be performed. Furthermore, early sex hormone treatment is necessary to induce and maintain typical pubertal development and to achieve optimal bone mineral accumulation. Pregnancy is possible via ova donation, and outcomes are similar to women with 46,XX ovarian failure.
SUMMARY: Further pathogenic gene mutations are likely to be identified, and the function, interaction and phenotypic effects of new and existing mutations will be further defined. Patients require long-term follow-up in specialist centres.

Brower MA, Jones MR, Rotter JI, et al.
Further investigation in europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals.
J Clin Endocrinol Metab. 2015; 100(1):E182-6 [PubMed] Free Access to Full Article Related Publications
CONTEXT: Two genome-wide association studies (GWAS) of polycystic ovary syndrome (PCOS) have identified 11 susceptibility loci in Chinese individuals. Some of the risk loci identified in Chinese cohorts, mostly from the first GWAS, have been replicated in Europeans. Replication of the loci from the second GWAS in European cohorts is necessary to determine whether the same variants confer risk for PCOS in multiple ethnicities.
OBJECTIVE: The objective of the study was to determine the effects of the Chinese GWAS loci in European-origin individuals.
DESIGN: This was a genetic association study.
SETTING: The study was conducted at a tertiary care academic center.
PATIENTS: Eight hundred forty-five European subjects with PCOS and 845 controls participated in the study.
INTERVENTIONS: INTERVENTIONS included blood sampling and genotyping.
MAIN OUTCOME MEASURE: The association between PCOS and 12 independent single-nucleotide polymorphisms mapping to seven of the Chinese GWAS loci in a European cohort was measured.
RESULTS: Variants in DENND1A (P = .0002), THADA (P = .035), FSHR (P = .007), and INSR (P = .046) were associated with PCOS in Europeans. The genetic risk score, generated for each subject based on the total number of risk alleles, was associated with the diagnosis of PCOS (P < .0001) and remained associated (P = .02), even after exclusion of the four variants individually associated with PCOS.
CONCLUSIONS: At least four of the PCOS susceptibility loci identified in the Chinese GWAS are associated with PCOS in Europeans. The overall genetic burden for PCOS, as demonstrated by the risk score, is also associated with the diagnosis of PCOS in Europeans. The PCOS susceptibility loci identified in the Chinese GWAS are thus likely to play an important role in the etiology of PCOS across ethnicities.

Singhasena W, Pantasri T, Piromlertamorn W, et al.
Follicle-stimulating hormone receptor gene polymorphism in chronic anovulatory women, with or without polycystic ovary syndrome: a cross-sectional study.
Reprod Biol Endocrinol. 2014; 12:86 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Polymorphisms at codons 307 and 680 are the most commonly encountered allelic variants of the follicle-stimulating hormone receptor (FSHR) gene. Studies in Caucasians suggest that certain FSHR variants are more common in women with polycystic ovary syndrome (PCOS) than normal women. The objective of this study was to determine the distribution of FSHR gene polymorphisms at codons 307 and 680 in Thai women with chronic anovulation, without (121 women) and with PCOS (133 women), using 132 known fertile women as controls.
METHODS: DNA samples from peripheral blood lymphocytes were extracted and analyzed by polymerase chain reaction-restriction fragment length polymorphism.
RESULTS: The prevalence of Threonine307Threonine (TT), Threonine307Alanine (TA), and Alanine307Alanine (AA) genotypes at codon 307 was 53.0% (95% CI = 44.2-61.7%), 42.4% (95% CI = 34-51.3%), and 4.5% (95% CI = 1.9-10.1%) in controls; 52.6% (95% CI = 43.8-61.3%), 39.8% (95% CI = 31.6-48.7%), and 7.5% (95% CI = 3.9-13.7%) in PCOS women; and 50.4% (95% CI = 42.8-61.2%), 45.4% (95% CI = 34.9-53.1%), and 4.5% (95% CI = 1.5-9.6%) in anovulatory women without PCOS, respectively. The prevalence of Asparagine680Asparagine (NN), Asparagine680Serine (NS), and Serine680Serine (SS) genotypes at codon 680 was 54.5% (95% CI = 45.7-63.2%), 40.9% (95% CI = 32.5-49.8%), and 4.5% (95% CI = 1.9-10.1%) in controls; 51.9% (95% CI = 43.1-60.6%), 44.4% (95% CI = 35.8-53.2%), and 3.8% (95% CI = 1.4-9.0%) in PCOS women; and 47.9% (95% CI = 40.4-58.8%), 47.1% (95% CI = 36.5-54.7%), and 5.0% (95% CI = 2-10.9%) in anovulatory women without PCOS, respectively. The prevalence of FSHR gene polymorphisms at both codons were not statistically different among the three groups.
CONCLUSIONS: In Thai women, there was no association between the FSHR gene polymorphism at codons 307 and 680 and chronic anovulation.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. FSHR, Cancer Genetics Web: http://www.cancer-genetics.org/FSHR.htm Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 01 September, 2019     Cancer Genetics Web, Established 1999