The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Gnrh1  -  gonadotropin releasing hormone 1

Mus musculus

Synonyms: Gnrh, Gnrh2, LHRH, LNRH, Lhrh1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Gnrh1


Psychiatry related information on Gnrh1


High impact information on Gnrh1

  • Remarkably, and in contrast to established notions on the nature of LHRH neuronal inputs, our data identify major olfactory projection pathways originating from a discrete population of olfactory sensory neurons but fail to document any synaptic connectivity with the vomeronasal system [9].
  • Injection of conditional pseudorabies virus into the brain of an LHRH::CRE mouse line led to the identification of neuronal networks connected to LHRH neurons [9].
  • In order to gain insight into sensory processing modulating reproductive behavioral and endocrine changes, we have aimed at identifying afferent pathways to neurons synthesizing luteinizing hormone-releasing hormone (LHRH, also known as gonadotropin-releasing hormone [GnRH]), a key neurohormone of reproduction [9].
  • Leuprorelin, a lutenizing hormone-releasing hormone (LHRH) agonist that reduces testosterone release from the testis, rescued motor dysfunction and nuclear accumulation of mutant androgen receptors in male transgenic mice [10].
  • Neurons expressing luteinizing hormone-releasing hormone (LHRH), found in the septal-preoptic nuclei and hypothalamus, control the release of gonadotropic hormones from the anterior pituitary gland and facilitate reproductive behaviour [11].

Chemical compound and disease context of Gnrh1

  • Thytrotopin-releasing hormone (TRH), for example, antagonizes the sedation and hypothermia produced by barbiturate and other depressant drugs and de Wied has shown that ACTH 4-10, TRH, LHRH and certain related substances show some activity in inhibition of extinction of a pole-jumping avoidance response in the rat [12].
  • Luteinizing Hormone Releasing Hormone (LHRH) agonists exert both "in vitro" and "in vivo" a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines [13].
  • BACKGROUND: Receptors for luteinizing hormone-releasing hormone (LHRH) on human prostate cancers can be used for targeted chemotherapy with cytotoxic analogs of LHRH, such as AN-207, which consists of superactive doxorubicin derivative 2-pyrrolino doxorubicin (AN-201) linked to carrier [D-Lys6] LHRH [14].
  • OBJECTIVES: A combination of flutamide (Eulexin) or nilutamide (Anandron) with a luteinizing hormone-releasing hormone (LHRH) agonist or orchiectomy is the only therapy demonstrated to prolong life in prostate cancer [15].
  • The efficacy of therapy with targeted cytotoxic luteinizing hormone-releasing hormone (LHRH) analog AN-207 consisting of superactive doxorubicin derivative AN-201 linked to carrier [D-Lys(6)]LH-RH was evaluated in vivo in nude mice bearing xenografts of MDA-PCa-2b prostate cancer line [16].

Biological context of Gnrh1


Anatomical context of Gnrh1


Associations of Gnrh1 with chemical compounds

  • GnRH stimulation of gonadotropin expression and secretion occurs through the G-protein-linked phospholipase C/inositol triphosphate intracellular signaling pathway, which ultimately leads to protein kinase C (PKC) activation and increased intracellular calcium levels [23].
  • Gonadotropin or androgen action was not, however, a prerequisite for the basal expression of GATA-4 or GATA-6 in the testis, as their presence in Sertoli and Leydig cells was demonstrated in genetically hypogonadal hpg mice, in rats treated with GnRH receptor antagonist, and in Sertoli cells after chemical abolition of Leydig cells [24].
  • Since the induction of galanin-IR in GnRH cells is more pronounced in OVX and proestrous mice, the expression of galanin-IR in GnRH cells in mice appears to be an activation-dependent phenomenon rather than a direct effect of estrogen [25].
  • Our studies indicate that DHEA has direct effects on GnRH transcription that appear to be unique from those observed after conversion to other steroidogenic compounds [26].
  • The levels of human FSH beta mRNA in monolayer cultures of pituitary cells were decreased by 24-hour treatments with 10 nM testosterone propionate or 5 alpha-dihydrotestosterone to 13 and 26% of control values, respectively, in the absence of GnRH [27].
  • In voltage clamp, the selective M-channel blocker, XE-991, inhibited a K(+) current in GnRH neurons [28].
  • Tetrodotoxin did not alter the Kp-induced GnRH release, indicating that Kp can act directly at the GnRH nerve terminals [29].

Physical interactions of Gnrh1

  • SRp30c specifically binds to both ESE3 and ESE4, whereas 9G8 binds to an element in exon 3 and strongly enhances the excision of GnRH intron A in the presence of minimal amount of other nuclear components [19].
  • These data define a novel cis-regulatory element comprised of an overlapping SBE and newly characterized non-consensus AP-1 binding sequence that integrates the stimulatory transcriptional effects of both GnRH and activin on the mGnRHR gene [30].
  • In this study, we used the alphaT3 gonadotrope cell line as a model to characterize the IGF-1R signaling pathways and to investigate whether this receptor interacts with the LHRH cascade [31].
  • Egr-1/MGRE binding was induced by GnRH in an ERK-dependent manner [32].
  • The increased binding of 125I-[His5,D-Tyr6] GnRH has allowed the development of a sensitive GnRH receptor binding assay for analysis of mutant GnRH receptors that exhibit decreased ligand binding [33].

Enzymatic interactions of Gnrh1

  • Immunohistochemical staining with a TH monoclonal antibody coupled with confocal microscopy was employed on vibratome-cut brain sections of female GnRH-green fluorescent protein (GFP) transgenic mice to evaluate possible appositions between GnRH and tuberoinfundibular dopaminergic (TIDA) neurons [34].

Regulatory relationships of Gnrh1

  • Furthermore, GnRH stimulated Egr-1 but not SF-1 expression in LbetaT2 cells [35].
  • In contrast, agonist stimulation of GnRH receptors expressed in HEK293 cells caused sustained phosphorylation and nuclear translocation of ERK1/2 by a protein kinase C-dependent but EGFR-independent pathway [36].
  • 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 [37].
  • To investigate the functional significance of gonadotrope CRH-BP, we examined the molecular mechanisms underlying GnRH-regulated CRH-BP expression in alphaT3-1 gonadotrope-like cells [38].
  • The transcription factor activator protein-2 (AP-2alpha) was differentially expressed and was present in the developmentally younger LHRH neuron [39].

Other interactions of Gnrh1

  • These cells synthesize alpha-subunit and gonadotropin-releasing hormone (GnRH) receptor, yet are not fully differentiated in that they do not synthesize the beta-subunits of luteinizing hormone (LH) or follicle-stimulating hormone (FSH) [40].
  • These results indicate that the duration of ERK1/2 activation depends on the signaling pathways utilized by GnRH in specific target cells [36].
  • Mutation of either Egr-1 or SF-1 elements within the LHbeta promoter attenuated this stimulation, whereas mutation of both promoter elements abrogated GnRH induction of the LHbeta promoter [35].
  • Here, we report that expression patterns of the Msx and Dlx families of homeodomain transcription factors largely coincide with the migratory route of GnRH neurons and co-express with GnRH in neurons during embryonic development [18].
  • The cis-regulatory element localized to position -292/-285 of the mouse GnRH receptor (mGnRHR) gene promoter, designated Sequence Underlying Responsiveness to GnRH 1 (SURG-1), has been shown previously to contribute to stimulation of mGnRHR gene expression by GnRH [37].

Analytical, diagnostic and therapeutic context of Gnrh1


  1. Effects of galanin-like peptide (GALP) on locomotion, reproduction, and body weight in female and male mice. Kauffman, A.S., Buenzle, J., Fraley, G.S., Rissman, E.F. Hormones and behavior. (2005) [Pubmed]
  2. Mechanisms of Disease: the first kiss-a crucial role for kisspeptin-1 and its receptor, G-protein-coupled receptor 54, in puberty and reproduction. Seminara, S.B. Nature clinical practice. Endocrinology & metabolism. (2006) [Pubmed]
  3. 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]
  4. 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]
  5. Transplanted gonadotropin-releasing hormone neurons promote pulsatile luteinizing hormone secretion in congenitally hypogonadal (hpg) male mice. Kokoris, G.J., Lam, N.Y., Ferin, M., Silverman, A.J., Gibson, M.J. Neuroendocrinology (1988) [Pubmed]
  6. Reduction of GnRH and infertility in the R6/2 mouse model of Huntington's disease. Papalexi, E., Persson, A., Björkqvist, M., Petersén, A., Woodman, B., Bates, G.P., Sundler, F., Mulder, H., Brundin, P., Popovic, N. Eur. J. Neurosci. (2005) [Pubmed]
  7. Localized and discrete changes in neuropeptide (LHRH and TRH) and neurotransmitter (NE and DA) concentrations within the olfactory bulbs of male mice as a function of social interaction. Dluzen, D.E., Ramirez, V.D. Hormones and behavior. (1983) [Pubmed]
  8. Luteinizing hormone modulates cognition and amyloid-beta deposition in Alzheimer APP transgenic mice. Casadesus, G., Webber, K.M., Atwood, C.S., Pappolla, M.A., Perry, G., Bowen, R.L., Smith, M.A. Biochim. Biophys. Acta (2006) [Pubmed]
  9. Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Yoon, H., Enquist, L.W., Dulac, C. Cell (2005) [Pubmed]
  10. Leuprorelin rescues polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Katsuno, M., Adachi, H., Doyu, M., Minamiyama, M., Sang, C., Kobayashi, Y., Inukai, A., Sobue, G. Nat. Med. (2003) [Pubmed]
  11. Origin of luteinizing hormone-releasing hormone neurons. Schwanzel-Fukuda, M., Pfaff, D.W. Nature (1989) [Pubmed]
  12. Comparison of the analeptic potency of TRH, ACTH 4-10, LHRH, and related peptides. Bissette, G., Nemeroff, C.B., Loosen, P.T., Prange, A.J., Lipton, M.A. Pharmacol. Biochem. Behav. (1976) [Pubmed]
  13. Effects of LHRH agonists on the growth of human prostatic tumor cells: "in vitro" and "in vivo" studies. Montagnani Marelli, M., Moretti, R.M., Dondi, D., Limonta, P., Motta, M. Archivio italiano di urologia, andrologia : organo ufficiale [di] Società italiana di ecografia urologica e nefrologica / Associazione ricerche in urologia. (1997) [Pubmed]
  14. Inhibition of human experimental prostate cancers by a targeted cytotoxic luteinizing hormone-releasing hormone analog AN-207. Stangelberger, A., Schally, A.V., Nagy, A., Szepeshazi, K., Kanashiro, C.A., Halmos, G. Prostate (2006) [Pubmed]
  15. Comparison of in vitro effects of the pure antiandrogens OH-flutamide, Casodex, and nilutamide on androgen-sensitive parameters. Simard, J., Singh, S.M., Labrie, F. Urology (1997) [Pubmed]
  16. Inhibition of in vivo proliferation of MDA-PCa-2b human prostate cancer by a targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207. Plonowski, A., Schally, A.V., Nagy, A., Groot, K., Krupa, M., Navone, N.M., Logothetis, C. Cancer Lett. (2002) [Pubmed]
  17. Maintenance of Spermatogenesis by the Activated Human (Asp567Gly) FSH Receptor During Testicular Regression Due to Hormonal Withdrawal. Allan, C.M., Garcia, A., Spaliviero, J., Jimenez, M. Biol. Reprod. (2006) [Pubmed]
  18. Developmental regulation of gonadotropin-releasing hormone gene expression by the MSX and DLX homeodomain protein families. Givens, M.L., Rave-Harel, N., Goonewardena, V.D., Kurotani, R., Berdy, S.E., Swan, C.H., Rubenstein, J.L., Robert, B., Mellon, P.L. J. Biol. Chem. (2005) [Pubmed]
  19. Cooperative actions of Tra2alpha with 9G8 and SRp30c in the RNA splicing of the gonadotropin-releasing hormone gene transcript. Park, E., Han, J., Son, G.H., Lee, M.S., Chung, S., Park, S.H., Park, K., Lee, K.H., Choi, S., Seong, J.Y., Kim, K. J. Biol. Chem. (2006) [Pubmed]
  20. Alpha-fetoprotein controls female fertility and prenatal development of the gonadotropin-releasing hormone pathway through an antiestrogenic action. De Mees, C., Laes, J.F., Bakker, J., Smitz, J., Hennuy, B., Van Vooren, P., Gabant, P., Szpirer, J., Szpirer, C. Mol. Cell. Biol. (2006) [Pubmed]
  21. Polysialic acid facilitates migration of luteinizing hormone-releasing hormone neurons on vomeronasal axons. Yoshida, K., Rutishauser, U., Crandall, J.E., Schwarting, G.A. J. Neurosci. (1999) [Pubmed]
  22. A novel AP-1 site is critical for maximal induction of the follicle-stimulating hormone beta gene by gonadotropin-releasing hormone. Coss, D., Jacobs, S.B., Bender, C.E., Mellon, P.L. J. Biol. Chem. (2004) [Pubmed]
  23. Egr-1 is a downstream effector of GnRH and synergizes by direct interaction with Ptx1 and SF-1 to enhance luteinizing hormone beta gene transcription. Tremblay, J.J., Drouin, J. Mol. Cell. Biol. (1999) [Pubmed]
  24. Expression and regulation of transcription factors GATA-4 and GATA-6 in developing mouse testis. Ketola, I., Rahman, N., Toppari, J., Bielinska, M., Porter-Tinge, S.B., Tapanainen, J.S., Huhtaniemi, I.T., Wilson, D.B., Heikinheimo, M. Endocrinology (1999) [Pubmed]
  25. Expression of galanin immunoreactivity in gonadotropin-releasing hormone neurons in mice: a confocal microscopic study. Rajendren, G., Gibson, M.J. Brain Res. (1999) [Pubmed]
  26. Evidence that dehydroepiandrosterone, DHEA, directly inhibits GnRH gene expression in GT1-7 hypothalamic neurons. Cui, H., Lin, S.Y., Belsham, D.D. Mol. Cell. Endocrinol. (2003) [Pubmed]
  27. Hormonal regulation of human follicle-stimulating hormone-beta subunit gene expression: GnRH stimulation and GnRH-independent androgen inhibition. Kumar, T.R., Low, M.J. Neuroendocrinology (1995) [Pubmed]
  28. Gonadotropin-releasing hormone (GnRH) activates the m-current in GnRH neurons: an autoregulatory negative feedback mechanism? Xu, C., Roepke, T.A., Zhang, C., Rønnekleiv, O.K., Kelly, M.J. Endocrinology (2008) [Pubmed]
  29. Kisspeptin can stimulate gonadotropin-releasing hormone (GnRH) release by a direct action at GnRH nerve terminals. d'Anglemont de Tassigny, X., Fagg, L.A., Carlton, M.B., Colledge, W.H. Endocrinology (2008) [Pubmed]
  30. Direct binding of AP-1 (Fos/Jun) proteins to a SMAD binding element facilitates both gonadotropin-releasing hormone (GnRH)- and activin-mediated transcriptional activation of the mouse GnRH receptor gene. Norwitz, E.R., Xu, S., Xu, J., Spiryda, L.B., Park, J.S., Jeong, K.H., McGee, E.A., Kaiser, U.B. J. Biol. Chem. (2002) [Pubmed]
  31. The luteinizing hormone-releasing hormone inhibits the anti-apoptotic activity of insulin-like growth factor-1 in pituitary alphaT3 cells by protein kinase Calpha-mediated negative regulation of Akt. Rose, A., Froment, P., Perrot, V., Quon, M.J., LeRoith, D., Dupont, J. J. Biol. Chem. (2004) [Pubmed]
  32. An early growth response protein (Egr) 1 cis-element is required for gonadotropin-releasing hormone-induced mitogen-activated protein kinase phosphatase 2 gene expression. Zhang, T., Wolfe, M.W., Roberson, M.S. J. Biol. Chem. (2001) [Pubmed]
  33. 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]
  34. A confocal microscopic study of gonadotropin-releasing hormone (GnRH) neuron inputs to dopaminergic neurons containing estrogen receptor alpha in the arcuate nucleus of GnRH-green fluorescent protein transgenic mice. Mitchell, V., Loyens, A., Spergel, D.J., Flactif, M., Poulain, P., Tramu, G., Beauvillain, J.C. Neuroendocrinology (2003) [Pubmed]
  35. Activation of luteinizing hormone beta gene by gonadotropin-releasing hormone requires the synergy of early growth response-1 and steroidogenic factor-1. Dorn, C., Ou, Q., Svaren, J., Crawford, P.A., Sadovsky, Y. J. Biol. Chem. (1999) [Pubmed]
  36. Roles of Src and epidermal growth factor receptor transactivation in transient and sustained ERK1/2 responses to gonadotropin-releasing hormone receptor activation. Shah, B.H., Farshori, M.P., Jambusaria, A., Catt, K.J. J. Biol. Chem. (2003) [Pubmed]
  37. 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]
  38. Gonadotropin-releasing hormone (GnRH) positively regulates corticotropin-releasing hormone-binding protein expression via multiple intracellular signaling pathways and a multipartite GnRH response element in alphaT3-1 cells. Westphal, N.J., Seasholtz, A.F. Mol. Endocrinol. (2005) [Pubmed]
  39. Transcription factor activator protein-2 is required for continued luteinizing hormone-releasing hormone expression in the forebrain of developing mice. Kramer, P.R., Krishnamurthy, R., Mitchell, P.J., Wray, S. Endocrinology (2000) [Pubmed]
  40. Immortalization of pituitary cells at discrete stages of development by directed oncogenesis in transgenic mice. Alarid, E.T., Windle, J.J., Whyte, D.B., Mellon, P.L. Development (1996) [Pubmed]
  41. Profiling neurotransmitter receptor expression in mouse gonadotropin-releasing hormone neurons using green fluorescent protein-promoter transgenics and microarrays. Todman, M.G., Han, S.K., Herbison, A.E. Neuroscience (2005) [Pubmed]
WikiGenes - Universities