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Gene Review

GNRHR  -  gonadotropin-releasing hormone receptor

Homo sapiens

Synonyms: GNRHR1, GRHR, GnRH receptor, GnRH-R, Gonadotropin-releasing hormone receptor, ...
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Disease relevance of GNRHR


Psychiatry related information on GNRHR


High impact information on GNRHR


Chemical compound and disease context of GNRHR


Biological context of GNRHR

  • Two blocks of strong linkage disequilibrium were identified that spanned GNRHR and one was identified spanning GNRH1; within each block, more than 80% of chromosomes carried one of a few common haplotypes [16].
  • Three SNPs in GNRHR showed modest association with late pubertal development in the trios; among the 506 women, a different SNP was associated with late menarche, and one rare haplotype was associated with early age of menarche [16].
  • We conclude that genetic variation in GNRH1 and GNRHR is not likely to be a substantial modulator of pubertal timing in the general population [16].
  • MAIN OUTCOME MEASURE(S): GNRHR mutations were characterized and compared with the phenotype [17].
  • INTERVENTION(S): DNA from 185 IHH patients were subjected to denaturing gradient gel electrophoresis for exons and splice junctions of the GNRHR gene [17].

Anatomical context of GNRHR


Associations of GNRHR with chemical compounds


Physical interactions of GNRHR


Enzymatic interactions of GNRHR

  • Calnexin did not affect receptor signaling when K(191) was deleted from the human WT GnRHR [27].

Regulatory relationships of GNRHR


Other interactions of GNRHR


Analytical, diagnostic and therapeutic context of GNRHR

  • Genomic DNA was amplified by PCR to obtain partially overlapping amplicons encompassing the exon-intron boundaries of the GnRHR and GPR54 genes and analyzed by single-stranded conformation polymorphism gel electrophoresis and/or DNA sequencing [33].
  • Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism [35].
  • Using RT-PCR and human pituitary poly(A)+ RNA as a template, the full-length GnRH receptor (wild type) and a second truncated cDNA characterized by a 128-bp deletion between nucleotide positions 522 and 651 were cloned [19].
  • Site-directed mutagenesis of nine nonconserved residues in the C-terminal domain of extracellular loop 2 of the human GnRH receptor showed that a minimum of two mutations (Val(5.24(197))Ala and Trp(5.32(205))His) is needed in this region for agonist activity of antagonist 135-18 [22].
  • In this study, confocal microscopy of fluorescently labeled GnRHR was used to show that the dominant-negative effect, which occurs for human (but not for rodent) GnRHR, results from WT receptor retention in the endoplasmic reticulum by mislocalized mutants [20].


  1. Mutational analysis of DAX1 in patients with hypogonadotropic hypogonadism or pubertal delay. Achermann, J.C., Gu, W.X., Kotlar, T.J., Meeks, J.J., Sabacan, L.P., Seminara, S.B., Habiby, R.L., Hindmarsh, P.C., Bick, D.P., Sherins, R.J., Crowley, W.F., Layman, L.C., Jameson, J.L. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  2. Immunolocalization of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Type I GnRH Receptor during Follicular Development in the Human Ovary. Choi, J.H., Gilks, C.B., Auersperg, N., Leung, P.C. J. Clin. Endocrinol. Metab. (2006) [Pubmed]
  3. Targeting of cytotoxic luteinizing hormone-releasing hormone analogs to breast, ovarian, endometrial, and prostate cancers. Nagy, A., Schally, A.V. Biol. Reprod. (2005) [Pubmed]
  4. Ability of luteinizing hormone releasing hormone-Pseudomonas aeruginosa exotoxin 40 binding to LHRH receptor on human liver cancer cells. Gong, S.L., Zhao, G., Zhao, H.G., Lu, W.T., Liu, G.W., Zhu, P. World J. Gastroenterol. (2004) [Pubmed]
  5. An activator protein 1-like motif mediates 17beta-estradiol repression of gonadotropin-releasing hormone receptor promoter via an estrogen receptor alpha-dependent mechanism in ovarian and breast cancer cells. Cheng, C.K., Chow, B.K., Leung, P.C. Mol. Endocrinol. (2003) [Pubmed]
  6. Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction. Costa, E.M., Bedecarrats, G.Y., Mendonca, B.B., Arnhold, I.J., Kaiser, U.B., Latronico, A.C. J. Clin. Endocrinol. Metab. (2001) [Pubmed]
  7. Gonadotropin-releasing hormone receptor gene expression in human ovary and granulosa-lutein cells. Minaretzis, D., Jakubowski, M., Mortola, J.F., Pavlou, S.N. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  8. A family with hypogonadotropic hypogonadism and mutations in the gonadotropin-releasing hormone receptor. de Roux, N., Young, J., Misrahi, M., Genet, R., Chanson, P., Schaison, G., Milgrom, E. N. Engl. J. Med. (1997) [Pubmed]
  9. Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans. Cheng, C.K., Leung, P.C. Endocr. Rev. (2005) [Pubmed]
  10. Gonadotropin-releasing hormone receptors. Millar, R.P., Lu, Z.L., Pawson, A.J., Flanagan, C.A., Morgan, K., Maudsley, S.R. Endocr. Rev. (2004) [Pubmed]
  11. Autosomal recessive idiopathic hypogonadotropic hypogonadism: genetic analysis excludes mutations in the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes. Bo-Abbas, Y., Acierno, J.S., Shagoury, J.K., Crowley, W.F., Seminara, S.B. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  12. The luteinizing hormone-releasing hormone receptor in human prostate cancer cells: messenger ribonucleic acid expression, molecular size, and signal transduction pathway. Limonta, P., Moretti, R.M., Marelli, M.M., Dondi, D., Parenti, M., Motta, M. Endocrinology (1999) [Pubmed]
  13. Suppression of a pituitary-ovarian axis by chronic oral administration of a novel nonpeptide gonadotropin-releasing hormone antagonist, TAK-013, in cynomolgus monkeys. Hara, T., Araki, H., Kusaka, M., Harada, M., Cho, N., Suzuki, N., Furuya, S., Fujino, M. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  14. GnRH receptors in human breast cancer and its contiguous not-involved breast tissue. Paradiso, A., Pezzetta, A., Cellamare, G., Schittulli, F., Marzullo, F., Reshkin, S.J. J. Endocrinol. Invest. (2000) [Pubmed]
  15. Evidence for coupling of phosphotyrosine phosphatase to gonadotropin-releasing hormone receptor in ovarian carcinoma membrane. Imai, A., Takagi, H., Furui, T., Horibe, S., Fuseya, T., Tamaya, T. Cancer (1996) [Pubmed]
  16. Determination of sequence variation and haplotype structure for the gonadotropin-releasing hormone (GnRH) and GnRH receptor genes: investigation of role in pubertal timing. Sedlmeyer, I.L., Pearce, C.L., Trueman, J.A., Butler, J.L., Bersaglieri, T., Read, A.P., Clayton, P.E., Kolonel, L.N., Henderson, B.E., Hirschhorn, J.N., Palmert, M.R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  17. The prevalence of gonadotropin-releasing hormone receptor mutations in a large cohort of patients with hypogonadotropic hypogonadism. Bhagavath, B., Ozata, M., Ozdemir, I.C., Bolu, E., Bick, D.P., Sherins, R.J., Layman, L.C. Fertil. Steril. (2005) [Pubmed]
  18. Agonist-induced endocytosis and recycling of the gonadotropin-releasing hormone receptor: effect of beta-arrestin on internalization kinetics. Vrecl, M., Anderson, L., Hanyaloglu, A., McGregor, A.M., Groarke, A.D., Milligan, G., Taylor, P.L., Eidne, K.A. Mol. Endocrinol. (1998) [Pubmed]
  19. Inhibition of gonadotropin-releasing hormone receptor signaling by expression of a splice variant of the human receptor. Grosse, R., Schöneberg, T., Schultz, G., Gudermann, T. Mol. Endocrinol. (1997) [Pubmed]
  20. Human loss-of-function gonadotropin-releasing hormone receptor mutants retain wild-type receptors in the endoplasmic reticulum: molecular basis of the dominant-negative effect. Brothers, S.P., Cornea, A., Janovick, J.A., Conn, P.M. Mol. Endocrinol. (2004) [Pubmed]
  21. Characterization of a new upstream GnRH receptor promoter in human ovarian granulosa-luteal cells. Cheng, C.K., Yeung, C.M., Chow, B.K., Leung, P.C. Mol. Endocrinol. (2002) [Pubmed]
  22. Two mutations in extracellular loop 2 of the human GnRH receptor convert an antagonist to an agonist. Ott, T.R., Troskie, B.E., Roeske, R.W., Illing, N., Flanagan, C.A., Millar, R.P. Mol. Endocrinol. (2002) [Pubmed]
  23. Complete hypogonadotropic hypogonadism associated with a novel inactivating mutation of the gonadotropin-releasing hormone receptor. Pralong, F.P., Gomez, F., Castillo, E., Cotecchia, S., Abuin, L., Aubert, M.L., Portmann, L., Gaillard, R.C. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  24. Steroidogenic factor-1 interacts with a gonadotrope-specific element within the first exon of the human gonadotropin-releasing hormone receptor gene to mediate gonadotrope-specific expression. Ngan, E.S., Cheng, P.K., Leung, P.C., Chow, B.K. Endocrinology (1999) [Pubmed]
  25. Mutations remote from the human gonadotropin-releasing hormone (GnRH) receptor-binding sites specifically increase binding affinity for GnRH II but not GnRH I: evidence for ligand-selective, receptor-active conformations. Lu, Z.L., Gallagher, R., Sellar, R., Coetsee, M., Millar, R.P. J. Biol. Chem. (2005) [Pubmed]
  26. Pivotal role for the cytoplasmic carboxyl-terminal tail of a nonmammalian gonadotropin-releasing hormone receptor in cell surface expression, ligand binding, and receptor phosphorylation and internalization. Blomenröhr, M., Heding, A., Sellar, R., Leurs, R., Bogerd, J., Eidne, K.A., Willars, G.B. Mol. Pharmacol. (1999) [Pubmed]
  27. Calnexin regulated gonadotropin-releasing hormone receptor plasma membrane expression. Brothers, S.P., Janovick, J.A., Conn, P.M. J. Mol. Endocrinol. (2006) [Pubmed]
  28. The LIM-homeodomain proteins Isl-1 and Lhx3 act with steroidogenic factor 1 to enhance gonadotrope-specific activity of the gonadotropin-releasing hormone receptor gene promoter. Granger, A., Bleux, C., Kottler, M.L., Rhodes, S.J., Counis, R., Laverrière, J.N. Mol. Endocrinol. (2006) [Pubmed]
  29. Expression and transcriptional regulation of the GnRH receptor gene in human neuronal cells. Yeung, C.M., An, B.S., Cheng, C.K., Chow, B.K., Leung, P.C. Mol. Hum. Reprod. (2005) [Pubmed]
  30. Coupling of GnRH concentration and the GnRH receptor-activated gene program. Yuen, T., Wurmbach, E., Ebersole, B.J., Ruf, F., Pfeffer, R.L., Sealfon, S.C. Mol. Endocrinol. (2002) [Pubmed]
  31. Targeted doxorubicin-containing luteinizing hormone-releasing hormone analogue AN-152 inhibits the growth of doxorubicin-resistant MX-1 human breast cancers. Bajo, A.M., Schally, A.V., Halmos, G., Nagy, A. Clin. Cancer Res. (2003) [Pubmed]
  32. Oct-1 is involved in the transcriptional repression of the gonadotropin-releasing hormone receptor gene. Cheng, C.K., Yeung, C.M., Hoo, R.L., Chow, B.K., Leung, P.C. Endocrinology (2002) [Pubmed]
  33. Role of sequence variations of the GnRH receptor and G protein-coupled receptor 54 gene in male idiopathic hypogonadotropic hypogonadism. Lanfranco, F., Gromoll, J., von Eckardstein, S., Herding, E.M., Nieschlag, E., Simoni, M. Eur. J. Endocrinol. (2005) [Pubmed]
  34. Conserved physical linkage of GnRH-R and RBM8 in the medaka and human genomes. Okubo, K., Mitani, H., Naruse, K., Kondo, M., Shima, A., Tanaka, M., Aida, K. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  35. Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism. Cerrato, F., Shagoury, J., Kralickova, M., Dwyer, A., Falardeau, J., Ozata, M., Van Vliet, G., Bouloux, P., Hall, J.E., Hayes, F.J., Pitteloud, N., Martin, K.A., Welt, C., Seminara, S.B. Eur. J. Endocrinol. (2006) [Pubmed]
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