Genomes and Genes
Summary: Cell surface proteins that bind FOLLICLE STIMULATING HORMONE with high affinity and trigger intracellular changes influencing the behavior of cells.
- Wunsch A, Ahda Y, Banaz Yaşar F, Sonntag B, Nieschlag E, Simoni M, et al. Single-nucleotide polymorphisms in the promoter region influence the expression of the human follicle-stimulating hormone receptor. Fertil Steril. 2005;84:446-53 pubmed..The newly identified SNPs do not seem to influence clinical parameters substantially, but modulate expression of the FSHR via changes in transcription factor binding sites. ..
- Inoue K, Nakamura K, Abe K, Hirakawa T, Tsuchiya M, Oomori Y, et al. Mechanisms of action of transforming growth factor beta on the expression of follicle-stimulating hormone receptor messenger ribonucleic acid levels in rat granulosa cells. Biol Reprod. 2003;69:1238-44 pubmed..Therefore, the profile of the TGFbeta effect on FSH-R mRNA granulosa cells may be caused by the increased stability of FSH-R mRNA and insensitivity to the follistatin. ..
- Asatiani K, Gromoll J, Eckardstein S, Zitzmann M, Nieschlag E, Simoni M. Distribution and function of FSH receptor genetic variants in normal men. Andrologia. 2002;34:172-6 pubmed..This clinical finding demonstrates that, differently from females, in whom a significant correlation between FSHR polymorphism and basal FSH levels was found, the FSHR genotype has no influence on clinical parameters in males. ..
- Shimoda C, Koh E, Yamamoto K, Matsui F, Sugimoto K, Sin H, et al. Single nucleotide polymorphism analysis of the follicle-stimulating hormone (FSH) receptor in Japanese with male infertility: identification of codon combination with heterozygous variations of the two discrete FSH receptor gene. Endocr J. 2009;56:859-65 pubmed..Dysfunction of the FSH receptor (FSHR) may be involved in some form of male infertility with azoospermia or oligozoospermia. We assessed the discrete codon combination with homo/heterozygous variation of the exon 10 in the FSHR gene...
- Grover A, Smith C, Gregory M, Cyr D, Sairam M, Hermo L. Effects of FSH receptor deletion on epididymal tubules and sperm morphology, numbers, and motility. Mol Reprod Dev. 2005;72:135-44 pubmed
- Behre H, Greb R, Mempel A, Sonntag B, Kiesel L, Kaltwasser P, et al. Significance of a common single nucleotide polymorphism in exon 10 of the follicle-stimulating hormone (FSH) receptor gene for the ovarian response to FSH: a pharmacogenetic approach to controlled ovarian hyperstimulation. Pharmacogenet Genomics. 2005;15:451-6 pubmed..In women undergoing controlled ovarian hyperstimulation, the p.N680S sequence variation results in lower oestradiol levels following FSH stimulation. This lower FSH receptor sensitivity can be overcome by higher FSH doses. ..
- Sundblad V, Chiauzzi V, Escobar M, Dain L, Charreau E. Screening of FSH receptor gene in Argentine women with premature ovarian failure (POF). Mol Cell Endocrinol. 2004;222:53-9 pubmed..We suggest that mutations in FSHR gene are rare in women with POF in Argentine. Presence of a particular FSHR isoform does not appear to be associated with this disease. ..
- Balla A, Danilovich N, Yang Y, Sairam M. Dynamics of ovarian development in the FORKO immature mouse: structural and functional implications for ovarian reserve. Biol Reprod. 2003;69:1281-93 pubmed..In addition, our data suggest that the FSH/receptor system is a major contributor to the formation and recruitment of the nongrowing pool of follicles as early as Postnatal Day 2 in the mouse. ..
- Tremoleda J, Tharasanit T, van Tol H, Stout T, Colenbrander B, Bevers M. Effects of follicular cells and FSH on the resumption of meiosis in equine oocytes matured in vitro. Reproduction. 2003;125:565-77 pubmed..These results demonstrate that the maintenance of meiotic arrest in equine oocytes during culture can be promoted by theca cells, which appear to act via a secreted inhibitory factor that cannot be suppressed or counteracted by FSH. ..
- Pengo M, Ferlin A, Arredi B, Ganz F, Selice R, Garolla A, et al. FSH receptor gene polymorphisms in fertile and infertile Italian men. Reprod Biomed Online. 2006;13:795-800 pubmed..The data showed that in the Italian population, FSHR genotypes have no influence on FSH concentrations both in normal and infertile males and do not associate with spermatogenetic impairment. ..
- Greb R, Grieshaber K, Gromoll J, Sonntag B, Nieschlag E, Kiesel L, et al. A common single nucleotide polymorphism in exon 10 of the human follicle stimulating hormone receptor is a major determinant of length and hormonal dynamics of the menstrual cycle. J Clin Endocrinol Metab. 2005;90:4866-72 pubmed..05). The FSH receptor Ser680/Ser680 genotype is associated with higher ovarian threshold to FSH, decreased negative feedback of luteal secretion to the pituitary during the intercycle transition, and longer menstrual cycles. ..
- Putowski L, Schillings W, Lee C, Reddy E, Jakowicki J. Human follicle-stimulating hormone receptor (FSH-R) promoter/enhancer activity is inhibited by transcriptional factors, from the upstream stimulating factors family, via E-box and newly identified initiator element (Inr) in FSH-R non-expressing cells. Gynecol Endocrinol. 2004;19:9-17 pubmed..USF family members inhibit FSH-R gene activity by acting via these elements. USF1 and USF2 suppress human FSH-R promoter/enhancer activity by acting on E-box 3. USF1 also decreases activity by interacting with the Inr element. ..
- Simoni M, Nieschlag E, Gromoll J. Isoforms and single nucleotide polymorphisms of the FSH receptor gene: implications for human reproduction. Hum Reprod Update. 2002;8:413-21 pubmed..The presence of SNPs in the FSH receptor gene capable of modifying FSH action paves the way for future patient-tailored, genotype-based hormone therapies. ..
- Fauser B, Diedrich K, Devroey P. Predictors of ovarian response: progress towards individualized treatment in ovulation induction and ovarian stimulation. Hum Reprod Update. 2008;14:1-14 pubmed..In this review, the methodology behind predictive factors and prediction models and their potential clinical applicability across ovulation induction and ovarian stimulation are explored. ..
- Kishi H, Krishnamurthy H, Galet C, Bhaskaran R, Ascoli M. Identification of a short linear sequence present in the C-terminal tail of the rat follitropin receptor that modulates arrestin-3 binding in a phosphorylation-independent fashion. J Biol Chem. 2002;277:21939-46 pubmed..We conclude that a short linear sequence present in the C-terminal tail of the rFSHR (642SATHNFHARK651) that is not phosphorylated limits internalization by lowering the affinity of the rFSHR for the endogenous non-visual arrestins. ..
- Bogerd J, Granneman J, Schulz R, Vischer H. Fish FSH receptors bind LH: how to make the human FSH receptor to be more fishy?. Gen Comp Endocrinol. 2005;142:34-43 pubmed..This paper intends to summarize the current situation with special emphasis to our comparative structure-function studies that aim at elucidating the molecular basis of ligand selectivity (in mammals) and ligand promiscuity (in fish). ..
- Laven J, Mulders A, Suryandari D, Gromoll J, Nieschlag E, Fauser B, et al. Follicle-stimulating hormone receptor polymorphisms in women with normogonadotropic anovulatory infertility. Fertil Steril. 2003;80:986-92 pubmed..Although this characteristic is associated with increased baseline FSH serum levels, altered ovarian sensitivity to exogenous FSH during ovulation induction could not be established. ..
- Jun J, Yoon J, Ku S, Choi Y, Hwang K, Park S, et al. Follicle-stimulating hormone receptor gene polymorphism and ovarian responses to controlled ovarian hyperstimulation for IVF-ET. J Hum Genet. 2006;51:665-70 pubmed..7 vs. 30.5%, P=0.013). The homozygous Ser/Ser genotype of FSHR polymorphism at position 680 may be associated with a reduced ovarian response to COH for IVF-ET, while Asn/Asn genotypes showed a higher pregnancy rate. ..
- De Castro F, Moron F, Montoro L, Galan J, Hernández D, Padilla E, et al. Human controlled ovarian hyperstimulation outcome is a polygenic trait. Pharmacogenetics. 2004;14:285-93 pubmed..The existence of genetic heterogeneity is also suspected. ..
- Bobe J, Maugars G, Nguyen T, Rime H, Jalabert B. Rainbow trout follicular maturational competence acquisition is associated with an increased expression of follicle stimulating hormone receptor and insulin-like growth factor 2 messenger RNAs. Mol Reprod Dev. 2003;66:46-53 pubmed..These results indicate that FMC acquisition is associated with an increased expression of these gene products that may be useful markers of FMC. ..
- Dahia C, Rao A. Demonstration of follicle-stimulating hormone receptor in cauda epididymis of rat. Biol Reprod. 2006;75:98-106 pubmed..These results suggest the possibility of a role for FSH in regulating the growth of the epididymis. ..
- de Koning C, Benjamins T, Harms P, Homburg R, van Montfrans J, Gromoll J, et al. The distribution of FSH receptor isoforms is related to basal FSH levels in subfertile women with normal menstrual cycles. Hum Reprod. 2006;21:443-6 pubmed..5%). The N680S sequence variation of the FSH receptor is found in >75% of the cases with elevated basal FSH and suggests a higher FSH threshold. ..
- Daelemans C, Smits G, De Maertelaer V, Costagliola S, Englert Y, Vassart G, et al. Prediction of severity of symptoms in iatrogenic ovarian hyperstimulation syndrome by follicle-stimulating hormone receptor Ser680Asn polymorphism. J Clin Endocrinol Metab. 2004;89:6310-5 pubmed
- Tena Sempere M, Manna P, Huhtaniemi I. Molecular cloning of the mouse follicle-stimulating hormone receptor complementary deoxyribonucleic acid: functional expression of alternatively spliced variants and receptor inactivation by a C566T transition in exon 7 of the coding sequence. Biol Reprod. 1999;60:1515-27 pubmed..In addition, we provide evidence for mFSHR inactivation by a C566T transition in exon 7 of the coding sequence, thus paving the way for further development of animal models of hypergonadotropic ovarian failure. ..
- Krishnamurthy H, Kats R, Danilovich N, Javeshghani D, Sairam M. Intercellular communication between Sertoli cells and Leydig cells in the absence of follicle-stimulating hormone-receptor signaling. Biol Reprod. 2001;65:1201-7 pubmed..Studies are currently under way to understand the mechanisms underlying this phenomenon. ..
- Robert P, Amsellem S, Christophe S, Benifla J, Bellet D, Koman A, et al. Cloning and sequencing of the equine testicular follitropin receptor. Biochem Biophys Res Commun. 1994;201:201-7 pubmed publisher..Furthermore, a potential N-glycosylation site was detected at a position not encountered in other receptors. Northern blot analysis identified three transcripts of 4.2 kb, 2.3 kb and 1.0 kb in horse testis...
- van Tol H, van Eijk M, Mummery C, van den Hurk R, Bevers M. Influence of FSH and hCG on the resumption of meiosis of bovine oocytes surrounded by cumulus cells connected to membrana granulosa. Mol Reprod Dev. 1996;45:218-24 pubmed..This is supported by the fact that receptors for FSH, but not for LH, are transcribed in the cumulus and granulosa cells of these follicles. ..
- Lazari M, Liu X, Nakamura K, Benovic J, Ascoli M. Role of G protein-coupled receptor kinases on the agonist-induced phosphorylation and internalization of the follitropin receptor. Mol Endocrinol. 1999;13:866-78 pubmed..The finding that inhibitors of GRK2 and GRK6 impair phosphorylation, but only the inhibitors of GRK2 impair internalization, suggests that different GRKs have differential effects on receptor internalization. ..
- Houde A, Lambert A, Saumande J, Silversides D, Lussier J. Structure of the bovine follicle-stimulating hormone receptor complementary DNA and expression in bovine tissues. Mol Reprod Dev. 1994;39:127-35 pubmed..8 and 2.55 kb, and 3 minor transcripts of 3.8, 3.3, and 1.6 kb. Bovine granulosa cells cultured with porcine FSH (0, 2, 10 ng/ml) for 4 days showed a decrease in the steady state level of the FSHr mRNA.(ABSTRACT TRUNCATED AT 250 WORDS) ..
- Tilly J, Aihara T, Nishimori K, Jia X, Billig H, Kowalski K, et al. Expression of recombinant human follicle-stimulating hormone receptor: species-specific ligand binding, signal transduction, and identification of multiple ovarian messenger ribonucleic acid transcripts. Endocrinology. 1992;131:799-806 pubmed..These results demonstrate the expression of functional hFSH receptor with unique ligand specificity and provide new data on the biochemical properties of the human receptor at the mRNA and protein levels. ..
- Sairam M, Krishnamurthy H. The role of follicle-stimulating hormone in spermatogenesis: lessons from knockout animal models. Arch Med Res. 2001;32:601-8 pubmed..This might pave the way for treatment of male infertility and contraception...
- Romero C, Paredes A, Dissen G, Ojeda S. Nerve growth factor induces the expression of functional FSH receptors in newly formed follicles of the rat ovary. Endocrinology. 2002;143:1485-94 pubmed
- Kishi H, Ascoli M. Multiple distant amino acid residues present in the serpentine region of the follitropin receptor modulate the rate of agonist-induced internalization. J Biol Chem. 2000;275:31030-7 pubmed
- Krishnamurthy H, Babu P, Morales C, Sairam M. Delay in sexual maturity of the follicle-stimulating hormone receptor knockout male mouse. Biol Reprod. 2001;65:522-31 pubmed..Based on these data we suggest that the FORKO mouse might be a useful experimental model to define the molecular mechanisms that underlie the delay in puberty. ..
- Aittomaki K, Lucena J, Pakarinen P, Sistonen P, Tapanainen J, Gromoll J, et al. Mutation in the follicle-stimulating hormone receptor gene causes hereditary hypergonadotropic ovarian failure. Cell. 1995;82:959-68 pubmed..We conclude that the mutation causes ODG in these families. ..
- Gromoll J, Brocker M, Derwahl M, Hoppner W. Detection of mutations in glycoprotein hormone receptors. Methods. 2000;21:83-97 pubmed..This article focuses, therefore, on patient selection and techniques for the detection of mutations of glycoprotein hormone receptors, and compiles useful laboratory protocols to conduct such studies. ..
- Simoni M, Gromoll J, Nieschlag E. The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr Rev. 1997;18:739-73 pubmed
- Marion S, Robert F, Crepieux P, Martinat N, Troispoux C, Guillou F, et al. G protein-coupled receptor kinases and beta arrestins are relocalized and attenuate cyclic 3',5'-adenosine monophosphate response to follicle-stimulating hormone in rat primary Sertoli cells. Biol Reprod. 2002;66:70-6 pubmed..These results highlight the relationship existing between the GRK/beta-arrestin regulatory system and the FSH-R signaling machinery in a physiological model. ..
- Gromoll J, Gudermann T, Nieschlag E. Molecular cloning of a truncated isoform of the human follicle stimulating hormone receptor. Biochem Biophys Res Commun. 1992;188:1077-83 pubmed
- Kumar R, Ijiri S, Trant J. Molecular biology of the channel catfish gonadotropin receptors: 2. Complementary DNA cloning, functional expression, and seasonal gene expression of the follicle-stimulating hormone receptor. Biol Reprod. 2001;65:710-7 pubmed..coded for a 662-amino acid protein that was most identical (51%-59%) to salmon gonadotropin receptor I and the FSH receptors of higher vertebrates, and less identical to LH receptors and thyrotropin receptors (45%-49% and 46%-47%, ..
- Patsoula E, Loutradis D, Drakakis P, Kallianidis K, Bletsa R, Michalas S. Expression of mRNA for the LH and FSH receptors in mouse oocytes and preimplantation embryos. Reproduction. 2001;121:455-61 pubmed
- Krishnamurthy H, Danilovich N, Morales C, Sairam M. Qualitative and quantitative decline in spermatogenesis of the follicle-stimulating hormone receptor knockout (FORKO) mouse. Biol Reprod. 2000;62:1146-59 pubmed..These data allow us to conclude that genetic disruption of FSH receptor signaling in the rodent induces major changes that might contribute to reduced fertility. ..
- Conway G, Conway E, Walker C, Hoppner W, Gromoll J, Simoni M. Mutation screening and isoform prevalence of the follicle stimulating hormone receptor gene in women with premature ovarian failure, resistant ovary syndrome and polycystic ovary syndrome. Clin Endocrinol (Oxf). 1999;51:97-9 pubmed..Polymorphisms of the FSH receptor gene do not appear to have pathophysiological significance with regard to ovarian function. ..
- Schmierer B, Schuster M, Shkumatava A, Kuchler K. Activin and follicle-stimulating hormone signaling are required for long-term culture of functionally differentiated primary granulosa cells from the chicken ovary. Biol Reprod. 2003;68:620-7 pubmed..Our data demonstrate that activin signaling is necessary to sustain a morphologically differentiated phenotype of cGC in vitro. The results also suggest a pivotal importance of activin signaling for granulosa cell function in vivo. ..
- Ciesiółka S, Budna J, Jopek K, Bryja A, Kranc W, Borys S, et al. Time- and Dose-Dependent Effects of 17 Beta-Estradiol on Short-Term, Real-Time Proliferation and Gene Expression in Porcine Granulosa Cells. Biomed Res Int. 2017;2017:9738640 pubmed publisher..Furthermore, the GC-luteal cell transformation in vitro may be significantly accompanied by the proliferative activity of GCs in pigs. ..
- Kaiser U. The pathogenesis of the ovarian hyperstimulation syndrome. N Engl J Med. 2003;349:729-32 pubmed
- Blumenfeld Z. Effect of FSH priming on response to hCG in subjects with follicle stimulating hormone receptor (FSHR) mutations. Fertil Steril. 2003;79:238-9; author reply 239 pubmed
- Eckardstein S, Schmidt A, Kamischke A, Simoni M, Gromoll J, Nieschlag E. CAG repeat length in the androgen receptor gene and gonadotrophin suppression influence the effectiveness of hormonal male contraception. Clin Endocrinol (Oxf). 2002;57:647-55 pubmed..5 times higher in men having more than 22 CAG repeats. In summary, our analysis shows that in a subset of men, effective hormonal male contraception can be achieved even in the absence of complete gonadotrophin suppression. ..
- Simoni M, Santi D, Negri L, Hoffmann I, Muratori M, Baldi E, et al. Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: a pharmacogenetic study. Hum Reprod. 2016;31:1960-9 pubmed publisher..MS received additional grants from Merck Serono and IBSA as well as honoraria from Merck Serono. The remaining authors declare that no conflicts of interest are present. EudraCT number 2010-020240-35. ..
- Dahia C, Rao A. Regulation of FSH receptor, PKIbeta, IL-6 and calcium mobilization: Possible mediators of differential action of FSH. Mol Cell Endocrinol. 2006;247:73-81 pubmed..It was also observed that FSH up (1.4-fold) regulates the levels of expression of IL-6 mRNA only in the immature rat Sertoli cells suggesting the possibility of its involvement in FSH regulated Sertoli cell proliferation. ..
- Forde N, Mihm M, Canty M, Zielak A, Baker P, Park S, et al. Differential expression of signal transduction factors in ovarian follicle development: a functional role for betaglycan and FIBP in granulosa cells in cattle. Physiol Genomics. 2008;33:193-204 pubmed publisher..Inhibition of genes for betaglycan and FIBP in granulosa cells in vitro suggests that they inhibit estradiol production in regressing subordinate follicles. ..
- Chu S, Rushdi S, Zumpe E, Mamers P, Healy D, Jobling T, et al. FSH-regulated gene expression profiles in ovarian tumours and normal ovaries. Mol Hum Reprod. 2002;8:426-33 pubmed..Comparison of the gene expression profiles between each tumour group suggests a molecular phenotype for GCT that is similar to that reported for FSH stimulated pre-ovulatory granulosa cells. ..