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Gene Review

Gnrhr  -  gonadotropin releasing hormone receptor

Mus musculus

Synonyms: GnRH receptor, GnRH-R, Gonadotropin-releasing hormone receptor
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Disease relevance of Gnrhr


High impact information on Gnrhr


Biological context of Gnrhr

  • The absence of a carboxyl-terminal cytoplasmic domain indicates the importance of other regions of the GnRH receptor in agonist-induced signal transduction, and possibly in receptor desensitization and sequestration [11].
  • Analysis of the kinetics of recovery of ERK inducibility after cholesterol normalization supported the conclusion that reestablishment of the association of the GnRHR and ERKs with the membrane raft compartment was not sufficient for reconstitution of signaling activity [12].
  • To understand these mechanisms in more depth, we generated transgenic mice bearing the 3.3-kb rat GnRH-R promoter linked to the human placental alkaline phosphatase reporter gene [13].
  • Contained within this region are three elements important for expression in alphaT3-1 cells: a Steroidogenic Factor-1 binding site (SF-1), an Activator Protein-1(AP-1) element, and an element termed the GnRH receptor activating sequence or GRAS [14].
  • Several potential protein kinase C phosphorylation sites which might mediate heterologous desensitization are present on the GnRH receptor [15].

Anatomical context of Gnrhr


Associations of Gnrhr with chemical compounds

  • Oct-1 and nuclear factor Y bind to the SURG-1 element to direct basal and gonadotropin-releasing hormone (GnRH)-stimulated mouse GnRH receptor gene transcription [20].
  • When secretion was stimulated on day 4 with 54 mM [K+] pulses, bypassing the GnRH-R, the LH-secretory response indicated that the GnRH pulse history as well as estradiol and dexamethasone have actions on L beta T2-secretory capacity distinct from changes in the GnRH-R [17].
  • An analysis of the role of this conserved residue (Leu(237)) in GnRH receptor function revealed that the binding affinities of the L237I and L237V mutant receptors were unchanged, but their abilities to mediate GnRH-induced inositol phosphate signaling, G protein coupling, and agonist-induced internalization were significantly impaired [21].
  • Mediation of cyclic AMP signaling by the first intracellular loop of the gonadotropin-releasing hormone receptor [22].
  • These findings indicate that cAMP signaling from the GnRH receptor is dependent on specific residues in the 1i loop that are not essential for activation of the phosphoinositide signaling pathway [22].

Physical interactions of Gnrhr


Regulatory relationships of Gnrhr


Other interactions of Gnrhr

  • MATERIALS AND METHODS: Hoxa10 and Gnrhr deficient mice were intercrossed with Insl3 transgenic mice [1].
  • RESULTS: Transgenic over expression of Insl3 failed to restore normal testicular descent in Hoxa10 or Gnrhr deficient males [1].
  • Overexpression of NF-YA increased GnRHR promoter activity, whereas expression of a dominant negative NF-YA mutant decreased activity, further supporting a role of NF-Y in regulation of mGnRHR gene transcription [20].
  • Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11 [18].
  • These findings indicate that the conserved apolar residue (Leu(237)) in the third intracellular loop is an important determinant of GnRH receptor expression and activation, and possibly that of other G protein-coupled receptors [21].

Analytical, diagnostic and therapeutic context of Gnrhr


  1. Over expression of insulin-like 3 does not prevent cryptorchidism in GNRHR or HOXA10 deficient mice. Feng, S., Bogatcheva, N.V., Truong, A., Engel, W., Adham, I.M., Agoulnik, A.I. J. Urol. (2006) [Pubmed]
  2. The gonadotropin-releasing hormone receptor gene promoter directs pituitary-specific oncogene expression in transgenic mice. Albarracin, C.T., Frosch, M.P., Chin, W.W. Endocrinology (1999) [Pubmed]
  3. Activin and glucocorticoids synergistically activate follicle-stimulating hormone beta-subunit gene expression in the immortalized LbetaT2 gonadotrope cell line. McGillivray, S.M., Thackray, V.G., Coss, D., Mellon, P.L. Endocrinology (2007) [Pubmed]
  4. Induction of apoptotic or lytic death in an ovarian adenocarcinoma cell line by antibodies generated against a synthetic N-terminal extracellular domain gonadotropin-releasing hormone receptor peptide. Ackerman, R.C., Johnson, G.A., Van Kirk, E.A., Asirvatham, A.L., Murdoch, W.J. Cancer Lett. (1994) [Pubmed]
  5. A novel mouse model of hypogonadotrophic hypogonadism: N-ethyl-N-nitrosourea-induced gonadotropin-releasing hormone receptor gene mutation. Pask, A.J., Kanasaki, H., Kaiser, U.B., Conn, P.M., Janovick, J.A., Stockton, D.W., Hess, D.L., Justice, M.J., Behringer, R.R. Mol. Endocrinol. (2005) [Pubmed]
  6. Mutations in gonadotropin-releasing hormone receptor gene cause hypogonadotropic hypogonadism. Layman, L.C., Cohen, D.P., Jin, M., Xie, J., Li, Z., Reindollar, R.H., Bolbolan, S., Bick, D.P., Sherins, R.R., Duck, L.W., Musgrove, L.C., Sellers, J.C., Neill, J.D. Nat. Genet. (1998) [Pubmed]
  7. Essential role of the homeodomain for pituitary homeobox 1 activation of mouse gonadotropin-releasing hormone receptor gene expression through interactions with c-Jun and DNA. Jeong, K.H., Chin, W.W., Kaiser, U.B. Mol. Cell. Biol. (2004) [Pubmed]
  8. The expression of gonadotropin-releasing hormone and its receptor in endometrial cancer, and its relevance as an autocrine growth factor. Chatzaki, E., Bax, C.M., Eidne, K.A., Anderson, L., Grudzinskas, J.G., Gallagher, C.J. Cancer Res. (1996) [Pubmed]
  9. Steroid receptor coactivator-3 is required for progesterone receptor trans-activation of target genes in response to gonadotropin-releasing hormone treatment of pituitary cells. An, B.S., Selva, D.M., Hammond, G.L., Rivero-Muller, A., Rahman, N., Leung, P.C. J. Biol. Chem. (2006) [Pubmed]
  10. Regulation of G protein-coupled receptor trafficking by inefficient plasma membrane expression: molecular basis of an evolved strategy. Janovick, J.A., Knollman, P.E., Brothers, S.P., Ayala-Yáñez, R., Aziz, A.S., Conn, P.M. J. Biol. Chem. (2006) [Pubmed]
  11. Molecular cloning and expression of cDNA encoding the murine gonadotropin-releasing hormone receptor. Reinhart, J., Mertz, L.M., Catt, K.J. J. Biol. Chem. (1992) [Pubmed]
  12. Signaling Complexes Associated with the Type I Gonadotropin-Releasing Hormone (GnRH) Receptor: Colocalization of Extracellularly Regulated Kinase 2 and GnRH Receptor within Membrane Rafts. Bliss, S.P., Navratil, A.M., Breed, M., Skinner, D.C., Clay, C.M., Roberson, M.S. Mol. Endocrinol. (2007) [Pubmed]
  13. The promoter of the rat gonadotropin-releasing hormone receptor gene directs the expression of the human placental alkaline phosphatase reporter gene in gonadotrope cells in the anterior pituitary gland as well as in multiple extrapituitary tissues. Granger, A., Ngô-Muller, V., Bleux, C., Guigon, C., Pincas, H., Magre, S., Daegelen, D., Tixier-Vidal, A., Counis, R., Laverrière, J.N. Endocrinology (2004) [Pubmed]
  14. Is gonadotrope expression of the gonadotropin releasing hormone receptor gene mediated by autocrine/paracrine stimulation of an activin response element? Duval, D.L., Ellsworth, B.S., Clay, C.M. Endocrinology (1999) [Pubmed]
  15. Absence of rapid desensitization of the mouse gonadotropin-releasing hormone receptor. Davidson, J.S., Wakefield, I.K., Millar, R.P. Biochem. J. (1994) [Pubmed]
  16. Parallel regulation of membrane trafficking and dominant-negative effects by misrouted gonadotropin-releasing hormone receptor mutants. Knollman, P.E., Janovick, J.A., Brothers, S.P., Conn, P.M. J. Biol. Chem. (2005) [Pubmed]
  17. Steroid and pulsatile gonadotropin-releasing hormone (GnRH) regulation of luteinizing hormone and GnRH receptor in a novel gonadotrope cell line. Turgeon, J.L., Kimura, Y., Waring, D.W., Mellon, P.L. Mol. Endocrinol. (1996) [Pubmed]
  18. Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13.1-q21.1 and mouse chromosome 5. Kaiser, U.B., Dushkin, H., Altherr, M.R., Beier, D.R., Chin, W.W. Genomics (1994) [Pubmed]
  19. Immunolocalization of a gonadotropin-releasing hormone receptor site in murine endometrium that mediates apoptosis. Murdoch, W.J. Cell Tissue Res. (1995) [Pubmed]
  20. Oct-1 and nuclear factor Y bind to the SURG-1 element to direct basal and gonadotropin-releasing hormone (GnRH)-stimulated mouse GnRH receptor gene transcription. Kam, K.Y., Jeong, K.H., Norwitz, E.R., Jorgensen, E.M., Kaiser, U.B. Mol. Endocrinol. (2005) [Pubmed]
  21. Expression and function of the gonadotropin-releasing hormone receptor are dependent on a conserved apolar amino acid in the third intracellular loop. Chung, H.O., Yang, Q., Catt, K.J., Arora, K.K. J. Biol. Chem. (1999) [Pubmed]
  22. Mediation of cyclic AMP signaling by the first intracellular loop of the gonadotropin-releasing hormone receptor. Arora, K.K., Krsmanovic, L.Z., Mores, N., O'Farrell, H., Catt, K.J. J. Biol. Chem. (1998) [Pubmed]
  23. A high affinity gonadotropin-releasing hormone (GnRH) tracer, radioiodinated at position 6, facilitates analysis of mutant GnRH receptors. Flanagan, C.A., Fromme, B.J., Davidson, J.S., Millar, R.P. Endocrinology (1998) [Pubmed]
  24. The third intracellular loop of the rat gonadotropin-releasing hormone receptor couples the receptor to Gs- and G(q/11)-mediated signal transduction pathways: evidence from loop fragment transfection in GGH3 cells. Ulloa-Aguirre, A., Stanislaus, D., Arora, V., Väänänen, J., Brothers, S., Janovick, J.A., Conn, P.M. Endocrinology (1998) [Pubmed]
  25. Transcriptional regulation of the GnRH receptor gene by glucocorticoids. Maya-Núñez, G., Conn, P.M. Mol. Cell. Endocrinol. (2003) [Pubmed]
  26. Delayed activation of phospholipase D by gonadotropin-releasing hormone in a clonal pituitary gonadotrope cell line (alpha T3-1). Netiv, E., Liscovitch, M., Naor, Z. FEBS Lett. (1991) [Pubmed]
  27. Pituitary adenylate cyclase-activating polypeptide and cyclic adenosine 3',5'-monophosphate stimulate the promoter activity of the rat gonadotropin-releasing hormone receptor gene via a bipartite response element in gonadotrope-derived cells. Pincas, H., Laverrière, J.N., Counis, R. J. Biol. Chem. (2001) [Pubmed]
  28. Cyclical expression of GnRH and GnRH receptor mRNA in lymphoid organs. Jacobson, J.D., Crofford, L.J., Sun, L., Wilder, R.L. Neuroendocrinology (1998) [Pubmed]
  29. Detection of messenger RNA for gonadotropin-releasing hormone (GnRH) but not for GnRH receptors in mouse mammary glands. Ikeda, M., Taga, M., Sakakibara, H., Minaguchi, H., Vonderhaar, B.K. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  30. A new photoreactive antagonist cross-links to the N-terminal domain of the gonadotropin-releasing hormone receptor. Assefa, D., Pawson, A.J., McArdle, C.A., Millar, R.P., Flanagan, C.A., Roeske, R., Davidson, J.S. Mol. Cell. Endocrinol. (1999) [Pubmed]
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