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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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Review

The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review)

  • Authors:
    • Arturo Aguilar-Rojas
    • Marco Allan Pérez-Solis
    • Guadalupe Maya-Núñez
  • View Affiliations / Copyright

    Affiliations: Research Unit in Reproductive Medicine, Health Research Council, Hospital de Gineco-Obstetricia ‘Luis Castelazo Ayala’, Instituto Mexicano del Seguro Social, Mexico 01090, D.F., Mexico
  • Pages: 861-868
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    Published online on: January 19, 2016
       https://doi.org/10.3892/ijo.2016.3346
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Abstract

Recently, an increasing amount of evidence indicates that human gonadotropin-releasing hormone (hGnRH) and its receptor (hGnRHR) are important regulatory components not only to the reproduction process but also in the regulation of some cancer cell functions such as cell proliferation, in both hormone-dependent and -independent types of tumors. The hGnRHR is a naturally misfolded protein that is retained mostly in the endoplasmic reticulum; however, this mechanism can be overcome by treatment with several pharmacoperones, therefore, increasing the amount of receptors in the cell membrane. In addition, several reports indicate that the expression level of hGnRHR in tumor cells is even lower than in pituitary or gonadotrope cells. The signal transduction pathways activated by hGnRH in both gonadotrope and different cancer cell types are described in the present review. We also discuss how the rescue of misfolded receptors in tumor cells could be a promising strategy for cancer therapy.
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1 

Kakar SS and Jennes L: Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor mRNAs in various non-reproductive human tissues. Cancer Lett. 98:57–62. 1995. View Article : Google Scholar : PubMed/NCBI

2 

Liu F, Usui I, Evans LG, Austin DA, Mellon PL, Olefsky JM and Webster NJ: Involvement of both G(q/11) and G(s) proteins in gonadotropin-releasing hormone receptor-mediated signaling in L beta T2 cells. J Biol Chem. 277:32099–32108. 2002. View Article : Google Scholar : PubMed/NCBI

3 

Hamm HE: How activated receptors couple to G proteins. Proc Natl Acad Sci USA. 98:4819–4821. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Gilman AG: G proteins: Transducers of receptor-generated signals. Annu Rev Biochem. 56:615–649. 1987. View Article : Google Scholar : PubMed/NCBI

5 

Ford CE, Skiba NP, Bae H, Daaka Y, Reuveny E, Shekter LR, Rosal R, Weng G, Yang CS, Iyengar R, et al: Molecular basis for interactions of G protein betagamma subunits with effectors. Science. 280:1271–1274. 1998. View Article : Google Scholar : PubMed/NCBI

6 

Berridge MJ and Irvine RF: Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 312:315–321. 1984. View Article : Google Scholar : PubMed/NCBI

7 

Limor R, Ayalon D, Capponi AM, Childs GV and Naor Z: Cytosolic free calcium levels in cultured pituitary cells separated by centrifugal elutriation: Effect of gonadotropin-releasing hormone. Endocrinology. 120:497–503. 1987. View Article : Google Scholar : PubMed/NCBI

8 

Tse FW, Tse A, Hille B, Hille B, Horstmann H and Almers W: Local Ca2+ release from internal stores controls exocytosis in pituitary gonadotrophs. Neuron. 18:121–132. 1997. View Article : Google Scholar : PubMed/NCBI

9 

Naor Z, Harris D and Shacham S: Mechanism of GnRH receptor signaling: Combinatorial cross-talk of Ca2+ and protein kinase C. Front Neuroendocrinol. 19:1–19. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Kim Y, Han JM, Park JB, Lee SD, Oh YS, Chung C, Lee TG, Kim JH, Park SK, Yoo JS, et al: Phosphorylation and activation of phospholipase D1 by protein kinase C in vivo: Determination of multiple phosphorylation sites. Biochemistry. 38:10344–10351. 1999. View Article : Google Scholar : PubMed/NCBI

11 

Mitchell R, Robertson DN, Holland PJ, Collins D, Lutz EM and Johnson MS: ADP-ribosylation factor-dependent phospholipase D activation by the M3 muscarinic receptor. J Biol Chem. 278:33818–33830. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Kolch W, Heidecker G, Kochs G, Hummel R, Vahidi H, Mischak H, Finkenzeller G, Marmé D and Rapp UR: Protein kinase C alpha activates RAF-1 by direct phosphorylation. Nature. 364:249–252. 1993. View Article : Google Scholar : PubMed/NCBI

13 

Levi NL, Hanoch T, Benard O, Rozenblat M, Harris D, Reiss N, Naor Z and Seger R: Stimulation of Jun N-terminal kinase (JNK) by gonadotropin-releasing hormone in pituitary alpha T3-1 cell line is mediated by protein kinase C, c-Src, and CDC42. Mol Endocrinol. 12:815–824. 1998.PubMed/NCBI

14 

Mulvaney JM and Roberson MS: Divergent signaling pathways requiring discrete calcium signals mediate concurrent activation of two mitogen-activated protein kinases by gonadotropin-releasing hormone. J Biol Chem. 275:14182–14189. 2000. View Article : Google Scholar : PubMed/NCBI

15 

Seger R and Krebs EG: The MAPK signaling cascade. FASEB J. 9:726–735. 1995.PubMed/NCBI

16 

Maurer RA, Kim KE, Schoderbek WE, Roberson MS and Glenn DJ and Glenn DJ: Regulation of glycoprotein hormone alpha-subunit gene expression. Recent Prog Horm Res. 54:455–484; discussion 485. 1999.PubMed/NCBI

17 

Ben-Menahem D, Shraga-Levine Z, Limor R and Naor Z: Arachidonic acid and lipoxygenase products stimulate gonadotropin alpha-subunit mRNA levels in pituitary alpha T3-1 cell line: Role in gonadotropin releasing hormone action. Biochemistry. 33:12795–12799. 1994. View Article : Google Scholar : PubMed/NCBI

18 

Shraga-Levine Z, Ben-Menahem D and Naor Z: Arachidonic acid and lipoxygenase products stimulate protein kinase C beta mRNA levels in pituitary alpha T3-1 cell line: Role in gonadotropin-releasing hormone action. Biochem J. 316:667–670. 1996. View Article : Google Scholar : PubMed/NCBI

19 

Bliss SP, Navratil AM, Xie J and Roberson MS: GnRH signaling, the gonadotrope and endocrine control of fertility. Front Neuroendocrinol. 31:322–340. 2010. View Article : Google Scholar : PubMed/NCBI

20 

Miller RS, Wolfe A, He L, Radovick S and Wondisford FE: CREB binding protein (CBP) activation is required for luteinizing hormone beta expression and normal fertility in mice. Mol Cell Biol. 32:2349–2358. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Khadra A and Li YX: A model for the pulsatile secretion of gonadotropin-releasing hormone from synchronized hypothalamic neurons. Biophys J. 91:74–83. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Haisenleder DJ, Dalkin AC, Ortolano GA, Marshall JC and Shupnik MA: A pulsatile gonadotropin-releasing hormone stimulus is required to increase transcription of the gonadotropin subunit genes: Evidence for differential regulation of transcription by pulse frequency in vivo. Endocrinology. 128:509–517. 1991. View Article : Google Scholar : PubMed/NCBI

23 

Qayum A, Gullick W, Clayton RC, Sikora K and Waxman J and Waxman J: The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors. Br J Cancer. 62:96–99. 1990. View Article : Google Scholar : PubMed/NCBI

24 

Halmos G, Arencibia JM, Schally AV, Davis R and Bostwick DG: High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers. J Urol. 163:623–629. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Fekete M, Redding TW, Comaru-Schally AM, Pontes JE, Connelly RW, Srkalovic G and Schally AV: Receptors for luteinizing hormone-releasing hormone, somatostatin, prolactin, and epidermal growth factor in rat and human prostate cancers and in benign prostate hyperplasia. Prostate. 14:191–208. 1989. View Article : Google Scholar : PubMed/NCBI

26 

Limonta P, Dondi D, Moretti RM, Maggi R and Motta M: Antiproliferative effects of luteinizing hormone-releasing hormone agonists on the human prostatic cancer cell line LNCaP. J Clin Endocrinol Metab. 75:207–212. 1992.PubMed/NCBI

27 

Dondi D, Limonta P, Moretti RM, Marelli MM, Garattini E and Motta M: Antiproliferative effects of luteinizing hormone-releasing hormone (LHRH) agonists on human androgen-independent prostate cancer cell line DU 145: Evidence for an autocrine-inhibitory LHRH loop. Cancer Res. 54:4091–4095. 1994.PubMed/NCBI

28 

Redding TW and Schally AV: Inhibition of prostate tumor growth in two rat models by chronic administration of D-Trp6 analogue of luteinizing hormone-releasing hormone. Proc Natl Acad Sci USA. 78:6509–6512. 1981. View Article : Google Scholar : PubMed/NCBI

29 

Tolis G, Ackman D, Stellos A, Mehta A, Labrie F, Fazekas AT, Comaru-Schally AM and Schally AV: Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Proc Natl Acad Sci USA. 79:1658–1662. 1982. View Article : Google Scholar : PubMed/NCBI

30 

Koppán M, Nagy A, Schally AV, Plonowski A, Halmos G, Arencibia JM and Groot K: Targeted cytotoxic analog of luteinizing hormone-releasing hormone AN-207 inhibits the growth of PC-82 human prostate cancer in nude mice. Prostate. 38:151–158. 1999. View Article : Google Scholar : PubMed/NCBI

31 

Arencibia JM, Schally AV, Halmos G, Nagy A, Kiaris H and Klaris H: In vitro targeting of a cytotoxic analog of luteinizing hormone-releasing hormone AN-207 to ES-2 human ovarian cancer cells as demonstrated by microsatellite analyses. Anticancer Drugs. 12:71–78. 2001. View Article : Google Scholar : PubMed/NCBI

32 

Gnanapragasam VJ, Darby S, Khan MM, Lock WG, Robson CN and Leung HY and Leung HY: Evidence that prostate gonadotropin-releasing hormone receptors mediate an anti-tumourigenic response to analogue therapy in hormone refractory prostate cancer. J Pathol. 206:205–213. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Gründker C, Huschmand Nia A and Emons G: Gonadotropin-releasing hormone receptor-targeted gene therapy of gynecologic cancers. Mol Cancer Ther. 4:225–231. 2005.PubMed/NCBI

34 

Limonta P, Dondi D, Moretti RM, Fermo D, Garattini E and Motta M: Expression of luteinizing hormone-releasing hormone mRNA in the human prostatic cancer cell line LNCaP. J Clin Endocrinol Metab. 76:797–800. 1993.PubMed/NCBI

35 

Moretti RM, Marelli MM, Dondi D, Poletti A, Martini L, Motta M and Limonta P: Luteinizing hormone-releasing hormone agonists interfere with the stimulatory actions of epidermal growth factor in human prostatic cancer cell lines, LNCaP and DU 145. J Clin Endocrinol Metab. 81:3930–3937. 1996.PubMed/NCBI

36 

Marelli MM, Moretti RM, Dondi D, Motta M and Limonta P: Luteinizing hormone-releasing hormone agonists interfere with the mitogenic activity of the insulin-like growth factor system in androgen-independent prostate cancer cells. Endocrinology. 140:329–334. 1999.PubMed/NCBI

37 

Maudsley S, Davidson L, Pawson AJ, Chan R, López de Maturana R and Millar RP: Gonadotropin-releasing hormone (GnRH) antagonists promote proapoptotic signaling in peripheral reproductive tumor cells by activating a Galphai-coupling state of the type I GnRH receptor. Cancer Res. 64:7533–7544. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Kraus S, Levy G, Hanoch T, Naor Z and Seger R: Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: Role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways. Cancer Res. 64:5736–5744. 2004. View Article : Google Scholar : PubMed/NCBI

39 

Kraus S, Naor Z and Seger R: Gonadotropin-releasing hormone in apoptosis of prostate cancer cells. Cancer Lett. 234:109–123. 2006. View Article : Google Scholar : PubMed/NCBI

40 

Choi JH, Gilks CB, Auersperg N and Leung PC: Immuno-localization of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and type I GnRH receptor during follicular development in the human ovary. J Clin Endocrinol Metab. 91:4562–4570. 2006. View Article : Google Scholar : PubMed/NCBI

41 

Emons G, Ortmann O, Schulz KD and Schally AV: Growth-inhibitory actions of analogues of Luteinizing hormone releasing hormone on tumor cells. Trends Endocrinol Metab. 8:355–362. 1997. View Article : Google Scholar

42 

Völker P, Gründker C, Schmidt O, Schulz KD and Emons G: Expression of receptors for luteinizing hormone-releasing hormone in human ovarian and endometrial cancers: Frequency, autoregulation, and correlation with direct antiproliferative activity of luteinizing hormone-releasing hormone analogues. Am J Obstet Gynecol. 186:171–179. 2002. View Article : Google Scholar : PubMed/NCBI

43 

Emons G, Ortmann O, Becker M, Irmer G, Springer B, Laun R, Hölzel F, Schulz KD and Schally AV: High affinity binding and direct antiproliferative effects of LHRH analogues in human ovarian cancer cell lines. Cancer Res. 53:5439–5446. 1993.PubMed/NCBI

44 

Yano T, Pinski J, Halmos G, Szepeshazi K, Groot K and Schally AV: Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75. Proc Natl Acad Sci USA. 91:7090–7094. 1994. View Article : Google Scholar : PubMed/NCBI

45 

So WK, Cheng JC, Poon SL and Leung PC: Gonadotropin-releasing hormone and ovarian cancer: A functional and mechanistic overview. FEBS J. 275:5496–5511. 2008. View Article : Google Scholar : PubMed/NCBI

46 

Wilkinson SJ, Kucukmetin A, Cross P, Darby S, Gnanapragasam VJ, Calvert AH, Robson CN and Edmondson RJ: Expression of gonadotrophin releasing hormone receptor I is a favorable prognostic factor in epithelial ovarian cancer. Hum Pathol. 39:1197–1204. 2008. View Article : Google Scholar : PubMed/NCBI

47 

Imai A, Ohno T, Furui T, Takahashi K, Matsuda T and Tamaya T: Gonadotropin-releasing hormone stimulates phospholipase C but not protein phosphorylation/dephosphorylation in plasma membrane from human epithelial ovarian cancer. Int J Gynecol Cancer. 3:311–317. 1993. View Article : Google Scholar : PubMed/NCBI

48 

Shibata S, Sato H, Ota H, Karube A, Takahashi O and Tanaka T: Involvement of annexin V in antiproliferative effects of gonadotropin-releasing hormone agonists on human endometrial cancer cell line. Gynecol Oncol. 66:217–221. 1997. View Article : Google Scholar : PubMed/NCBI

49 

Kim KY, Choi KC, Auersperg N and Leung PC: Mechanism of gonadotropin-releasing hormone (GnRH)-I and -II-induced cell growth inhibition in ovarian cancer cells: Role of the GnRH-I receptor and protein kinase C pathway. Endocr Relat Cancer. 13:211–220. 2006. View Article : Google Scholar : PubMed/NCBI

50 

Kimura A, Ohmichi M, Kurachi H, Ikegami H, Hayakawa J, Tasaka K, Kanda Y, Nishio Y, Jikihara H, Matsuura N, et al: Role of mitogen-activated protein kinase/extracellular signal-regulated kinase cascade in gonadotropin-releasing hormone-induced growth inhibition of a human ovarian cancer cell line. Cancer Res. 59:5133–5142. 1999.PubMed/NCBI

51 

Imai A, Takagi H, Horibe S, Fuseya T and Tamaya T and Tamaya T: Coupling of gonadotropin-releasing hormone receptor to Gi protein in human reproductive tract tumors. J Clin Endocrinol Metab. 81:3249–3253. 1996.PubMed/NCBI

52 

Imai A, Horibe S, Takagi A and Tamaya T: Gi protein activation of gonadotropin-releasing hormone-mediated protein dephosphorylation in human endometrial carcinoma. Am J Obstet Gynecol. 176:371–376. 1997. View Article : Google Scholar : PubMed/NCBI

53 

Emons G, Muller V, Ortmann O, Grossmann G, Trautner U, Stuckrad B, Schulz K and Schally A: Luteinizing hormone-releasing hormone agonist triptorelin antagonizes signal transduction and mitogenic activity of epidermal growth factor in human ovarian and endometrial cancer cell lines. Int J Oncol. 9:1129–1137. 1996.PubMed/NCBI

54 

Gründker C, Völker P and Emons G: Antiproliferative signaling of luteinizing hormone-releasing hormone in human endometrial and ovarian cancer cells through G protein alpha(I)-mediated activation of phosphotyrosine phosphatase. Endocrinology. 142:2369–2380. 2001.PubMed/NCBI

55 

Shirahige Y, Cook C, Pinski J, Halmos G, Nair R and Schally A: Treatment with luteinizing-hormone-releasing hormone antagonist sb-75 decreases levels of epidermal growth-factor receptor and its messenger-RNA in ov-1063 human epithelial ovarian-cancer xenografts in nude-mice. Int J Oncol. 5:1031–1035. 1994.PubMed/NCBI

56 

Cho-Clark M, Larco DO, Semsarzadeh NN, Vasta F, Mani SK and Wu TJ: GnRH-(1–5) transactivates EGFR in Ishikawa human endometrial cells via an orphan G protein-coupled receptor. Mol Endocrinol. 28:80–98. 2014. View Article : Google Scholar

57 

Szabó I, Bősze S, Orbán E, Sipos É, Halmos G, Kovács M and Mező G: Comparative in vitro biological evaluation of daunorubicin containing GnRH-I and GnRH-II conjugates developed for tumor targeting. J Pept Sci. 21:426–435. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Cheang MC, Voduc D, Bajdik C, Leung S, McKinney S, Chia SK, Perou CM and Nielsen TO: Basal-like breast cancer defined by five biomarkers has superior prognostic value than triple-negative phenotype. Clin Cancer Res. 14:1368–1376. 2008. View Article : Google Scholar : PubMed/NCBI

59 

Gründker C, Föst C, Fister S, Nolte N, Günthert AR and Emons G: Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo. Breast Cancer Res. 12:R492010. View Article : Google Scholar : PubMed/NCBI

60 

Sedgley KR, Finch AR, Caunt CJ and McArdle CA: Intracellular gonadotropin-releasing hormone receptors in breast cancer and gonadotrope lineage cells. J Endocrinol. 191:625–636. 2006. View Article : Google Scholar : PubMed/NCBI

61 

Limonta P, Montagnani Marelli M, Mai S, Motta M, Martini L and Moretti RM: GnRH receptors in cancer: From cell biology to novel targeted therapeutic strategies. Endocr Rev. 33:784–811. 2012. View Article : Google Scholar : PubMed/NCBI

62 

Fekete M, Wittliff JL and Schally AV: Characteristics and distribution of receptors for [D-TRP6]-luteinizing hormone-releasing hormone, somatostatin, epidermal growth factor, and sex steroids in 500 biopsy samples of human breast cancer. J Clin Lab Anal. 3:137–147. 1989. View Article : Google Scholar

63 

Baumann KH, Kiesel L, Kaufmann M, Bastert G and Runnebaum B: Characterization of binding sites for a GnRH-agonist (buserelin) in human breast cancer biopsies and their distribution in relation to tumor parameters. Breast Cancer Res Treat. 25:37–46. 1993. View Article : Google Scholar : PubMed/NCBI

64 

Moriya T, Suzuki T, Pilichowska M, Ariga N, Kimura N, Ouchi N, Nagura H and Sasano H: Immunohistochemical expression of gonadotropin releasing hormone receptor in human breast carcinoma. Pathol Int. 51:333–337. 2001. View Article : Google Scholar : PubMed/NCBI

65 

Mangia A, Tommasi S, Reshkin SJ, Simone G, Stea B, Schittulli F and Paradiso A: Gonadotropin releasing hormone receptor expression in primary breast cancer: Comparison of immunohistochemical, radioligand and Western blot analyses. Oncol Rep. 9:1127–1132. 2002.PubMed/NCBI

66 

Morgan K, Meyer C, Miller N, Sims AH, Cagnan I, Faratian D, Harrison DJ, Millar RP and Langdon SP: GnRH receptor activation competes at a low level with growth signaling in stably transfected human breast cell lines. BMC Cancer. 11:4762011. View Article : Google Scholar : PubMed/NCBI

67 

Millar RP, Pawson AJ, Morgan K, Rissman EF and Lu ZL: Diversity of actions of GnRHs mediated by ligand-induced selective signaling. Front Neuroendocrinol. 29:17–35. 2008. View Article : Google Scholar

68 

Naor Z and Huhtaniemi I: Interactions of the GnRH receptor with heterotrimeric G proteins. Front Neuroendocrinol. 34:88–94. 2013. View Article : Google Scholar

69 

Sviridonov L, Dobkin-Bekman M, Shterntal B, Przedecki F, Formishell L, Kravchook S, Rahamim-Ben Navi L, Bar-Lev TH, Kazanietz MG, Yao Z, et al: Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines. Mol Cell Endocrinol. 369:107–118. 2013. View Article : Google Scholar : PubMed/NCBI

70 

Aguila r-Rojas A, Huer ta-Reyes M, Maya-Núñez G, Arechavaleta-Velásco F, Conn PM, Ulloa-Aguirre A and Valdés J: Gonadotropin-releasing hormone receptor activates GTPase RhoA and inhibits cell invasion in the breast cancer cell line MDA-MB-231. BMC Cancer. 12:5502012. View Article : Google Scholar

71 

Goodson AG and Grossman D: Strategies for early melanoma detection: Approaches to the patient with nevi. J Am Acad Dermatol. 60:719–735; quiz 736–718. 2009. View Article : Google Scholar : PubMed/NCBI

72 

Moretti RM, Mai S, Montagnani Marelli M, Bani MR, Ghilardi C, Giavazzi R, Taylor DM, Martini PG and Limonta P: Dual targeting of tumor and endothelial cells by gonadotropin-releasing hormone agonists to reduce melanoma angiogenesis. Endocrinology. 151:4643–4653. 2010. View Article : Google Scholar : PubMed/NCBI

73 

Wen J, Feng Y, Bjorklund CC, Wang M, Orlowski RZ, Shi ZZ, Liao B, O'Hare J, Zu Y, Schally AV, et al: Luteinizing Hormone-Releasing Hormone (LHRH)-I antagonist cetrorelix inhibits myeloma cell growth in vitro and in vivo. Mol Cancer Ther. 10:148–158. 2011. View Article : Google Scholar

74 

Ghiringhelli F, Isambert N and Ladoire S: Degarelix as a new antiangiogenic agent for metastatic colon cancer? World J Gastroenterol. 19:769–772. 2013. View Article : Google Scholar : PubMed/NCBI

75 

Schreier VN, Pethő L, Orbán E, Marquardt A, Petre BA, Mező G and Manea M: Protein expression profile of HT-29 human colon cancer cells after treatment with a cytotoxic daunorubicin-GnRH-III derivative bioconjugate. PLoS One. 9:e940412014. View Article : Google Scholar : PubMed/NCBI

76 

Carlson MJ, Thiel KW and Leslie KK: Past, present, and future of hormonal therapy in recurrent endometrial cancer. Int J Womens Health. 6:429–435. 2014.PubMed/NCBI

77 

Zhang J, Chtcheglova LA, Zhu R, Hinterdorfer P, Zhang B and Tang J: Nanoscale organization of human GnRH-R on human bladder cancer cells. Anal Chem. 86:2458–2464. 2014. View Article : Google Scholar : PubMed/NCBI

78 

Conn PM, Janovick JA, Brothers SP and Knollman PE: ‘Effective inefficiency’: Cellular control of protein trafficking as a mechanism of post-translational regulation. J Endocrinol. 190:13–16. 2006. View Article : Google Scholar : PubMed/NCBI

79 

Maya-Núñez G, Janovick JA and Conn PM: Combined modification of intracellular and extracellular loci on human gonadotropin-releasing hormone receptor provides a mechanism for enhanced expression. Endocrine. 13:401–407. 2000. View Article : Google Scholar

80 

Conn PM and Janovick JA: Drug development and the cellular quality control system. Trends Pharmacol Sci. 30:228–233. 2009. View Article : Google Scholar : PubMed/NCBI

81 

Janovick JA, Patny A, Mosley R, Goulet MT, Altman MD, Rush TS III, Cornea A and Conn PM: Molecular mechanism of action of pharmacoperone rescue of misrouted GPCR mutants: The GnRH receptor. Mol Endocrinol. 23:157–168. 2009. View Article : Google Scholar :

82 

Maya-Núñez G, Ulloa-Aguirre A, Janovick JA and Conn PM: Pharmacological chaperones correct misfolded GPCRs and rescue function: Protein trafficking as a therapeutic target. Subcell Biochem. 63:263–289. 2012. View Article : Google Scholar : PubMed/NCBI

83 

Maya-Núñez G, Janovick JA, Ulloa-Aguirre A, Söderlund D, Conn PM and Méndez JP: Molecular basis of hypogonadotropic hypogonadism: Restoration of mutant (E(90)K) GnRH receptor function by a deletion at a distant site. J Clin Endocrinol Metab. 87:2144–2149. 2002. View Article : Google Scholar : PubMed/NCBI

84 

Janovick JA, Maya-Nunez G and Conn PM: Rescue of hypogonadotropic hypogonadism-causing and manufactured GnRH receptor mutants by a specific protein-folding template: Misrouted proteins as a novel disease etiology and therapeutic target. J Clin Endocrinol Metab. 87:3255–3262. 2002. View Article : Google Scholar : PubMed/NCBI

85 

Conn PM and Ulloa-Aguirre A: Pharmacological chaperones for misfolded gonadotropin-releasing hormone receptors. Adv Pharmacol. 62:109–141. 2011. View Article : Google Scholar : PubMed/NCBI

86 

Janovick JA, Knollman PE, Brothers SP, Ayala-Yáñez R, Aziz AS and Conn PM: Regulation of G protein-coupled receptor trafficking by inefficient plasma membrane expression: Molecular basis of an evolved strategy. J Biol Chem. 281:8417–8425. 2006. View Article : Google Scholar : PubMed/NCBI

87 

Cheung LW and Wong AS: Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues. FEBS J. 275:5479–5495. 2008. View Article : Google Scholar : PubMed/NCBI

88 

Sánchez CA, Mercado AJ, Contreras HR, Cabezas JC, Huidobro CC and Castellón EA: Pharmacoperone IN3 enhances the apoptotic effect of leuprolide in prostate cancer cells by increasing the gonadotropin-releasing hormone receptor in the cell membrane. Anticancer Drugs. 23:959–969. 2012.PubMed/NCBI

89 

Fister S, Günthert AR, Aicher B, Paulini KW, Emons G and Gründker C: GnRH-II antagonists induce apoptosis in human endometrial, ovarian, and breast cancer cells via activation of stress-induced MAPKs p38 and JNK and proapoptotic protein Bax. Cancer Res. 69:6473–6481. 2009. View Article : Google Scholar : PubMed/NCBI

90 

Cheng CK and Leung PC: Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans. Endocr Rev. 26:283–306. 2005. View Article : Google Scholar

91 

Janovick JA, Stewart MD, Jacob D, Martin LD, Deng JM, Stewart CA, Wang Y, Cornea A, Chavali L, Lopez S, et al: Restoration of testis function in hypogonadotropic hypogonadal mice harboring a misfolded GnRHR mutant by pharmacoperone drug therapy. Proc Natl Acad Sci USA. 110:21030–21035. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Aguilar-Rojas A, Pérez-Solis MA and Maya-Núñez G: The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review). Int J Oncol 48: 861-868, 2016.
APA
Aguilar-Rojas, A., Pérez-Solis, M.A., & Maya-Núñez, G. (2016). The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review). International Journal of Oncology, 48, 861-868. https://doi.org/10.3892/ijo.2016.3346
MLA
Aguilar-Rojas, A., Pérez-Solis, M. A., Maya-Núñez, G."The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review)". International Journal of Oncology 48.3 (2016): 861-868.
Chicago
Aguilar-Rojas, A., Pérez-Solis, M. A., Maya-Núñez, G."The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review)". International Journal of Oncology 48, no. 3 (2016): 861-868. https://doi.org/10.3892/ijo.2016.3346
Copy and paste a formatted citation
x
Spandidos Publications style
Aguilar-Rojas A, Pérez-Solis MA and Maya-Núñez G: The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review). Int J Oncol 48: 861-868, 2016.
APA
Aguilar-Rojas, A., Pérez-Solis, M.A., & Maya-Núñez, G. (2016). The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review). International Journal of Oncology, 48, 861-868. https://doi.org/10.3892/ijo.2016.3346
MLA
Aguilar-Rojas, A., Pérez-Solis, M. A., Maya-Núñez, G."The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review)". International Journal of Oncology 48.3 (2016): 861-868.
Chicago
Aguilar-Rojas, A., Pérez-Solis, M. A., Maya-Núñez, G."The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review)". International Journal of Oncology 48, no. 3 (2016): 861-868. https://doi.org/10.3892/ijo.2016.3346
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