GnRH’a ve GnRH Antagonistlerin Etki Mekanizmaları

Wu HM, Chang HM, Leung PCK. Gonadotropin-releasing hormone analogs: Mechanisms of action and clinical applications in female reproduction Front Neuroendocrinol. 2021;60:100876. doi: 10.1016/j.yfrne.2020.100876. Epub 2020 Oct 9

Yang-Feng TL, Seeburg PH, Francke U. Human luteinizing hormone-releasing hormone gene (LHRH) is located on short arm of chromosome 8 (region 8p11.2––p21). Somat. Cell Mol. Genet. 1986 Jan;12(1):95-100.doi: 10.1007/BF01560732.

Radovick S, Wondisford FE, Nakayama Y, et al. Isolation and characterization of the human gonadotropin-releasing hormone gene in the hypothalamus and placenta. Mol. Endocrinol. 1990 Mar;4(3):476-80.doi: 10.1210/mend-4-3-476.

White RB, Eisen JA, Kasten TL, et al. Second gene for gonadotropin-releasing hormone in humans. Proc Natl Acad Sci USA. 1998 Jan 6;95(1):305-9.doi: 10.1073/pnas.95.1.305

Eicke N, Gunthert AR, Emons G, Grundker C. GnRH-II agonist [D-Lys6] GnRH-II inhibits the EGF-induced mitogenic signal transduction in human endometrial and ovarian cancer cells. Int. J. Oncol. 2006 Nov;29(5):1223-9.

Millar, R.P., 2003. GnRH II and type II GnRH receptors. Trends Endocrinol Metab. 2003 Jan;14(1):35-43.doi: 10.1016/s1043-2760(02)00016-4

Kaiser UB, Conn PM, Chin WW. Studies of gonadotropin-releasing hormone (GnRH) action using GnRH receptor-expressing pituitary cell lines. Endocr Rev. 1997 Feb;18(1):46-70.doi: 10.1210/edrv.18.1.0289.

Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002 Dec 6;298(5600):1911-2.doi: 10.1126/science.1072682.

Navratil AM, Bliss SP, Berghorn KA, et al. Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK. J. Biol. Chem. 2003 Aug 22;278(34):31593-602. doi: 10.1074/jbc.M304273200

Haisenleder DJ, Ferris HA, Shupnik MA. The calcium component of gonadotropin-releasing hormone-stimulated luteinizing hormone subunit gene transcription is mediated by calcium/calmodulin-dependent protein kinase type II. Endocrinology. 2003 Jun;144(6):2409-16. doi: 10.1210/en.2002-0013.

Burger LL, Haisenleder DJ, Aylor KW, et al. Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation. Biol Reprod. 2008 Nov;79(5):947-53. doi: 10.1095/biolreprod.108.070987. Epub 2008 Aug 20.

Pratap A, Garner KL, Voliotis M, et al. Mathematical modeling of gonadotropin-releasing hormone signaling. Mol. Cell Endocrinol. 2017 Jul 5:449:42-55.doi: 10.1016/j.mce.2016.08.022

Bradham C, McClay DR. p38 MAPK in development and cancer. Cell Cycle. 2006 Apr;5(8):824-8.doi: 10.4161/cc.5.8.2685. Epub 2006 Apr 17.

Seeburg PH, Mason AJ, Stewart TA,et al. The mammalian GnRH gene and its pivotal role in reproduction. Recent Prog Horm Res. 1987:43:69-98.doi: 10.1016/b978-0-12-571143-2.50008-3

15.Carmel PW, Araki S, Ferin M. Pituitary stalk portal blood collection in rhesus monkeys: evidence for pulsatile release of gonadotropin-releasing hormone (GnRH). Endocrinology. 1976;99:243–248. doi: 10.1210/endo-99-1-243.

16.Loumaye E, Catt KJ. Homologous regulation of gonadotropin-releasing hormone receptors in cultured pituitary cells. Science. 1982;215:983–985. doi:10.1126/science.6296998.

17.Mason DR, Arora KK, Mertz LM, Catt KJ. Homologous down-regulation of gonadotropin-releasing hormone receptor sites and messenger ribonucleic acid transcripts in alpha T3-1 cells. Endocrinology. 1994;135:1165–1170. doi: 10.1210/endo.135.3.8070359

18.Nett TM, Crowder ME, Moss GE, Duello TM. GnRH-receptor interaction. V. Down-regulation of pituitary receptors for GnRH in ovariectomized ewes by infusion of homologous hormone. Biol Reprod. 1981;24:1145–1155.

19.Pawson AJ, Faccenda E, Maudsley S, Lu ZL, Naor Z, Millar RP. Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization. Endocrinology. 2008;149:1415–1422. doi: 10.1210/en.2007-1159

20.Vrecl M, Heding A, Hanyaloglu A, Taylor PL, Eidne KA. Internalization kinetics of the gonadotropin-releasing hormone (GnRH) receptor. Pflugers Arch. 2000 Jan;439(Suppl 1):r019-r020.doi: 10.1007/s004240000075.

21.Manna C, Rahman A, Sbracia M, Pappalardo S, Mohamed EI, Linder R, Nardo LG. Serum luteinizing hormone, follicle-stimulating hormone and oestradiol pattern in women undergoing pituitary suppression with different gonadotrophin-releasing hormone analogue protocols for assisted reproduction. Gynecol.Endocrinol. 2005;20:188–194. doi: 10.1080/09513590400027141.

22.Rothman MS, Wierman ME. The role of gonadotropin releasing hormone in normal and pathologic endocrine processes. Curr Opin Endocrinol Diabetes Obes. 2007;14:306–310. doi: 10.1097/MED.0b013e3281e2c9fc

23. Bliss SP, Navratti AM, Xie J, Roberson MS. GnRH signaling, the gonadotrope and endocrine control of fertility. Front Neuroendocrinol. 2010 Jul;31(3):322-340.doi: 10.1016/j.yfrne.2010.04.002.

Smith JT, et al. Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology. 2005;146:3686–3692. doi: 10.1210/en.2005-0488.

Zoeller RT, Seeburg PH, Young WS., III In situ hybridization histochemistry for messenger ribonucleic acid (mRNA) encoding gonadotropin-releasing hormone (GnRH): effect of estrogen on cellular levels of GnRH mRNA in female rat brain. Endocrinology. 1988;122:2570–2577. doi: 10.1210/endo-122-6-2570.

Petersen SL, Ottem EN, Carpenter CD. Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol. Biol Reprod. 2003;69:1771–1778. doi: 10.1095/biolreprod.103.019745.

Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, Fadiel A, Leranth C, Vondracek-Klepper S, Lewis C, Chang A, Parducz A. Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge. Reprod Sci. 2007;14:101–116. doi: 10.1177/1933719107301059.

Estrada KM, Clay CM, Pompolo S, Smith JT, Clarke IJ. Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback. J Neuroendocrinol. 2006;18:806–809. doi: 10.1111/j.1365-2826.2006.01485.x.

Herbison AE. Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: the case for the rostral periventricular area of the third ventricle (RP3V) Brain Res Rev. 2008;57:277–287. doi: 10.1016/j.brainresrev.2007.05.006

Petersen SL, Ottem EN, Carpenter CD. Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol. Biol Reprod. 2003 Dec;69(6):1771-8.doi: 10.1095/biolreprod.103.019745.

Simonian SX, Spratt DP, Herbison AE. Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat. J Comp Neurol. 1999;411:346–358. doi: 10.1002/(sici)1096-9861(19990823)411:2<346::aid-cne13>3.0.co;2-s.

Demirol A, Bozdağ G, Gürgan T. GnRH Agonistleri Ve Antagonistleri: Güncel Yönleri. İnönü Üniversitesi Tıp Fakültesi Dergisi. 13(2) 135-140 (2006)

Cornea A, Janovick JA, Maya-Nunez G, Conn PM. Gonadotropin releasing hormone receptor microaggregation. Rate monitored by fluorescence resonance energy transfer. J Biol Chem. 2001;276(3):2153-2158. doi: 10.1074/jbc.M007850200. Epub 2000 Oct 16

Cornea A, Janovich JA, Lin X, Conn PM. Simultaneous and independent

visualization of the gonadotropin-releasing hormone receptor and

its ligand: evidence for independent processing and recycling in living cells. Endocrinology. 1999 September 140(9):4272-80. doi: 10.1210/endo.140.9.7049

Gordon K, Hodgen GD. GnRH agonists and antagonists in assisted reproduction. Balliere’s Clinical Obstet & Gynecol. 1992 Jun;6(2):247-65. doi: 10.1016/s0950-3552(05)80085-9

Kumar P, Sharma A. Gonadotropin-releasing hormone analogs: Understanding advantages and limitations. J. Hum. Reprod. Sci. 2014;7:170–174. doi: 10.4103/0974-1208.142476.

Matta, WH, Stabile I, Shaw RW, et al. Doppler assessment of uterine blood flow changes in patients with fibroids receiving the gonadotropin-releasing hormone agonist Buserelin. Fertil Steril. 1988 Jun;49(6):1083-5.doi: 10.1016/s0015-0282(16)59966-x.

Meresman GF, Bilotas MA, Lombardi E, et al. Effect of GnRH analogues on apoptosis and release of interleukin-1beta and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod 2003 Sep;18(9):1767-71.doi: 10.1093/humrep/deg356.

Wu HM, Cheng JC, Wang HS, et al. Gonadotropin-releasing hormone type II induces apoptosis of human endometrial cancer cells by activating GADD45alpha. Cancer Res. May 15;69(10):4202-8.doi: 10.1158/0008-5472.CAN-08-4591.

Abbara A, Jayasena CN, Christopoulos G,et al. Efficacy of Kisspeptin-54 to Trigger Oocyte Maturation in Women at High Risk of Ovarian Hyperstimulation Syndrome (OHSS) During In Vitro Fertilization (IVF) Therapy. J. Clin. Endocrinol. Metabol. 2015 Sep;100(9):3322-3331.doi: 10.1210/jc.2015-2332.Epub 2015 Jul 20.

Wu HM, Huang HY, Lee CL, et al. Gonadotropin-releasing hormone type II (GnRH-II) agonist regulates the motility of human decidual endometrial stromal cells: possible effect on embryo implantation and pregnancy. Biol. Reprod. 2015 Apr;92(4):98. doi: 10.1095/biolreprod.114.127324. Epub 2015 Mar 11.

Tafi E, Leone Roberti Maggiore U, Alessandri F, et al. Advances in pharmacotherapy for treating endometriosis. Expert Opin Pharmacother. 2015;16(16):2465-83. doi: 10.1517/14656566.2015.1085510. Epub 2015 Sep 7

Lee JH, Choi YS. The role of gonadotropin-releasing hormone agonists in female fertility preservation. Clin. Exp. Reprod. Med. 2021;48:11–26. doi: 10.5653/cerm.2020.04049.

Resta C, Moustogiannis A, Chatzinikita E,et al. Gonadotropin-Releasing Hormone (GnRH)/GnRH Receptors and Their Role in the Treatment of Endometriosis. Cureus. 2023;15:e38136. doi: 10.7759/cureus.38136.

Golan A. GnRH analogues in the treatment of uterine fibroids. Hum. Reprod. 1996;11((Suppl. S3)):33–41. doi: 10.1093/humrep/11.suppl_3.33.

Eugster EA. Treatment of Central Precocious Puberty. J. Endocr. Soc. 2019;3:965–972. doi: 10.1210/js.2019-00036.

Huerta-Reyes M, Maya-Nunez G, Perez-Solis MA,et al. Treatment of Breast Cancer With Gonadotropin-Releasing Hormone Analogs. Front. Oncol. 2019;9:943. doi: 10.3389/fonc.2019.00943.

Choi S, Lee AK. Efficacy and safety of gonadotropin-releasing hormone agonists used in the treatment of prostate cancer. Drug Healthc. Patient Saf. 2011;3:107–119. doi: 10.2147/DHPS.S24106

Surrey ES. GnRH agonists in the treatment of symptomatic endometriosis: A review. FS Rep. 2023;4:40–45. doi: 10.1016/j.xfre.2022.11.009.

Blumenfeld Z. How to preserve fertility in young women exposed to chemotherapy? The role of GnRH agonist cotreatment in addition to cryopreservation of embrya, oocytes, or ovaries. Oncologist 12, 1044–1054.

Newton CL, Riekert C, Millar RP. Gonadotropin-releasing hormone analog therapeutics. Minerva Ginecol. 2018 Oct;70(5):497-515. doi: 10.23736/S0026-4784.18.04316-2. Epub 2018 Sep 26.

Van Poppel H, Klotz L. Gonadotropin-releasing hormone: An update review of the antagonists versus agonists. Int. J. Urol. 2012;19:594–601. doi: 10.1111/j.1442-2042.2012.02997.x.

Weiss J.M., Diedrich K., Ludwig M. Gonadotropin-releasing hormone antagonists: Pharmacology and clinical use in women. Treat. Endocrinol. 2002;1:281–291. doi: 10.2165/00024677-200201050-00002.

Behre HM, Klein B, Steinmeyer E, et al. Effective suppression of luteinizing hormone and testosterone by single doses of the new gonadotropin-releasing hormone antagonist cetrorelix (SB-75) in normal men. J Clin Endocrinol Metab. 1992;75(2):393–398. doi: 10.1210/jcem.75.2.1639941

Kupker W, Felberbaum RE, Krapp M, et al. Use of GnRH antagonists in the treatment of endometriosis. Reprod Biomed Online 2002;5:12-16. doi: 10.1016/s1472-6483(10)61590-8

Todd NF, Lieberman R, Gulley JL, Dahut W, Arlen PM. Prolonged response to nilutamide in a patient with stage D0.5 prostate cancer who previously failed androgen deprivation therapy. Am J Ther 2005 Mar-Apr;12(2):172-4. doi: 10.1097/01.mjt.0000144497.85706.e6.

Resta C, Moustogiannis A, Chatzinikita E, et al. Gonadotropin-Releasing Hormone (GnRH)/GnRH Receptors and Their Role in the Treatment of Endometriosis. Cureus. 2023 Apr 26;15(4):e38136.doi: 10.7759/cureus.38136.eCollection 2023 Apr.

Golan A. GnRH analogues in the treatment of uterine fibroids. Hum. Reprod. 1996 Nov;11 Suppl 3:33-41. doi: 10.1093/humrep/11.suppl_3.33

Eugster EA. Treatment of Central Precocious Puberty. J. Endocr. Soc. 2019;3:965–972. doi: 10.1210/js.2019-00036

Huerta-Reyes M, Maya-Nunez G, Perez-Solis MA,et al. Treatment of Breast Cancer With Gonadotropin-Releasing Hormone Analogs. Front. Oncol. 2019 Oct 1:9:943.doi: 10.3389/fonc.2019.00943. eCollection 2019.

Weiss J.M., Ludwig M., Ortmann O., Diedrich K. GnRH antagonists in the treatment of infertility. Ann. Med. 2003;35:512–522. doi: 10.1080/07853890310001302.

Lindner C, Braendle W, Lichtenberg V, et al. Induction of pharmacological hypogonadotropism using gonadotropin-releasing hormone agonists in patients undergoing controlled ovarian stimulation.Gynecol Obstet Invest 1990;29(2):132-139. doi: 10.1159/000293319.

Varney NR, Syrop C, Kubu CS, et al. Neuropsychologic dysfunction in women following leuprolide acetate induction of hypoestrogenism. J Assist Reprod Genet 1993 Jan;10(1):53-57. doi: 10.1007/BF01204441.

Newton CR, Slota D, Yuzpe AA, et al. Memory complaints associated with the use of gonadotropin-releasing hormone agonists: a preliminary study. Fertil Steril 1996 Jun;65(6):1253-1255.doi: 10.1016/s0015-0282(16)58351-4.

Warnock JK, Bundren JC, Morris DW. Depressive mood symptoms associated with ovarian suppression. Fertil Steril. 2000 Nov;74(5):984-986.doi: 10.1016/s0015-0282(00)01607-1.

The North American Ganirelix Study Group. Efficacy and safety of ganirelix acetate versus leuprolide acetate in women undergoing controlled ovarian hyperstimulation. Fertil Steril 2001 Jan;75(1):38-45.doi: 10.1016/s0015-0282(00)01638-1.

Albano C, Felberbaum RE, Smitz J, et al. Controlled ovarian stimulation with HMG: results of a prospective randomized phase III European study comparing the LHRH-antagonist cetrorelix (cetrotide) and the LHRH-agonist Buserelin. Hum Reprod. 2000 Mar;15(3):526-531.doi: 10.1093/humrep/15.3.526.

Gordon K, Williams RF, Danforth DR, et al. A novel regimen of gonadotropin-releasing hormone (GnRH) antagonist plus pulsatile GnRH: controlled restoration of gonadotropin secretion and ovulation induction. Fertil Steril. 1990;54:1140–1145.

Itskovitz-Eldor J, Kol S, Mannaerts B. Use of a single bolus of GnRH agonist triptorelin to trigger ovulation after GnRH antagonist ganirelix treatment in women undergoing ovarian stimulation for assisted reproduction, with special reference to the prevention of ovarian hyperstimulation syndrome: a preliminary report. Hum Reprod. 2000 Sep;15(9):1965-1968. doi: 10.1093/humrep/15.9.1965.

Fauser BC, De Jong D, Olivennes F, et al. Endocrine profiles after triggering of final oocyte maturation with GnRH agonist after cotreatment with the GnRH antagonist ganirelix during ovarian hyperstimulation for in vitro fertilization. J Clin Endocr Metab. 2002 Feb;87(2):709-15.doi: 10.1210/jcem.87.2.8197.

Gordon K, Hodgen GD. Evolving role of gonadotropin-releasing hormone antagonists. Trends Endocrinol Metab. 1992 Sep;3(7):259-63.doi: 10.1016/1043-2760(92)90128-n.

Al-Inany HG, Abou-Setta AM, Aboulghar M. Gonadotrophin-releasing hormone antagonists for assisted conception. Cochrane Database Syst Rev. 2006 Jul 19:(3):CD001750. doi: 10.1002/14651858.CD001750.pub2.

Humaidan P, Polyzos NP, Alsbjerg B, et al. GnRHa trigger and individualized luteal phase hCG support according to ovarian response to stimulation: two prospective randomized controlled multi-centre studies in IVF patients. Hum. Reprod. 2013 Sep;28(9):2511-21. doi: 10.1093/humrep/det249. Epub 2013 Jun 9.

Castillo JC, Haahr T, Martinez-Moya M, et al. Gonadotropin-releasing hormone agonist ovulation trigger-beyond OHSS prevention. Ups J Med Sci. 2020 May;125(2):138-143. doi: 10.1080/03009734.2020.1737599.Epub 2020 Mar 25

Wu HM, Chang HM, Leung PCK. Gonadotropin-releasing hormone analogs: Mechanisms of action and clinical applications in female reproduction Front Neuroendocrinol. 2021;60:100876. doi: 10.1016/j.yfrne.2020.100876. Epub 2020 Oct 9

Yang-Feng TL, Seeburg PH, Francke U. Human luteinizing hormone-releasing hormone gene (LHRH) is located on short arm of chromosome 8 (region 8p11.2––p21). Somat. Cell Mol. Genet. 1986 Jan;12(1):95-100.doi: 10.1007/BF01560732.

Radovick S, Wondisford FE, Nakayama Y, et al. Isolation and characterization of the human gonadotropin-releasing hormone gene in the hypothalamus and placenta. Mol. Endocrinol. 1990 Mar;4(3):476-80.doi: 10.1210/mend-4-3-476.

White RB, Eisen JA, Kasten TL, et al. Second gene for gonadotropin-releasing hormone in humans. Proc Natl Acad Sci USA. 1998 Jan 6;95(1):305-9.doi: 10.1073/pnas.95.1.305

Eicke N, Gunthert AR, Emons G, Grundker C. GnRH-II agonist [D-Lys6] GnRH-II inhibits the EGF-induced mitogenic signal transduction in human endometrial and ovarian cancer cells. Int. J. Oncol. 2006 Nov;29(5):1223-9.

Millar, R.P., 2003. GnRH II and type II GnRH receptors. Trends Endocrinol Metab. 2003 Jan;14(1):35-43.doi: 10.1016/s1043-2760(02)00016-4

Kaiser UB, Conn PM, Chin WW. Studies of gonadotropin-releasing hormone (GnRH) action using GnRH receptor-expressing pituitary cell lines. Endocr Rev. 1997 Feb;18(1):46-70.doi: 10.1210/edrv.18.1.0289.

Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science. 2002 Dec 6;298(5600):1911-2.doi: 10.1126/science.1072682.

Navratil AM, Bliss SP, Berghorn KA, et al. Constitutive localization of the gonadotropin-releasing hormone (GnRH) receptor to low density membrane microdomains is necessary for GnRH signaling to ERK. J. Biol. Chem. 2003 Aug 22;278(34):31593-602. doi: 10.1074/jbc.M304273200

Haisenleder DJ, Ferris HA, Shupnik MA. The calcium component of gonadotropin-releasing hormone-stimulated luteinizing hormone subunit gene transcription is mediated by calcium/calmodulin-dependent protein kinase type II. Endocrinology. 2003 Jun;144(6):2409-16. doi: 10.1210/en.2002-0013.

Burger LL, Haisenleder DJ, Aylor KW, et al. Regulation of intracellular signaling cascades by GNRH pulse frequency in the rat pituitary: roles for CaMK II, ERK, and JNK activation. Biol Reprod. 2008 Nov;79(5):947-53. doi: 10.1095/biolreprod.108.070987. Epub 2008 Aug 20.

Pratap A, Garner KL, Voliotis M, et al. Mathematical modeling of gonadotropin-releasing hormone signaling. Mol. Cell Endocrinol. 2017 Jul 5:449:42-55.doi: 10.1016/j.mce.2016.08.022

Bradham C, McClay DR. p38 MAPK in development and cancer. Cell Cycle. 2006 Apr;5(8):824-8.doi: 10.4161/cc.5.8.2685. Epub 2006 Apr 17.

Seeburg PH, Mason AJ, Stewart TA,et al. The mammalian GnRH gene and its pivotal role in reproduction. Recent Prog Horm Res. 1987:43:69-98.doi: 10.1016/b978-0-12-571143-2.50008-3

15.Carmel PW, Araki S, Ferin M. Pituitary stalk portal blood collection in rhesus monkeys: evidence for pulsatile release of gonadotropin-releasing hormone (GnRH). Endocrinology. 1976;99:243–248. doi: 10.1210/endo-99-1-243.

16.Loumaye E, Catt KJ. Homologous regulation of gonadotropin-releasing hormone receptors in cultured pituitary cells. Science. 1982;215:983–985. doi:10.1126/science.6296998.

17.Mason DR, Arora KK, Mertz LM, Catt KJ. Homologous down-regulation of gonadotropin-releasing hormone receptor sites and messenger ribonucleic acid transcripts in alpha T3-1 cells. Endocrinology. 1994;135:1165–1170. doi: 10.1210/endo.135.3.8070359

18.Nett TM, Crowder ME, Moss GE, Duello TM. GnRH-receptor interaction. V. Down-regulation of pituitary receptors for GnRH in ovariectomized ewes by infusion of homologous hormone. Biol Reprod. 1981;24:1145–1155.

19.Pawson AJ, Faccenda E, Maudsley S, Lu ZL, Naor Z, Millar RP. Mammalian type I gonadotropin-releasing hormone receptors undergo slow, constitutive, agonist-independent internalization. Endocrinology. 2008;149:1415–1422. doi: 10.1210/en.2007-1159

20.Vrecl M, Heding A, Hanyaloglu A, Taylor PL, Eidne KA. Internalization kinetics of the gonadotropin-releasing hormone (GnRH) receptor. Pflugers Arch. 2000 Jan;439(Suppl 1):r019-r020.doi: 10.1007/s004240000075.

21.Manna C, Rahman A, Sbracia M, Pappalardo S, Mohamed EI, Linder R, Nardo LG. Serum luteinizing hormone, follicle-stimulating hormone and oestradiol pattern in women undergoing pituitary suppression with different gonadotrophin-releasing hormone analogue protocols for assisted reproduction. Gynecol.Endocrinol. 2005;20:188–194. doi: 10.1080/09513590400027141.

22.Rothman MS, Wierman ME. The role of gonadotropin releasing hormone in normal and pathologic endocrine processes. Curr Opin Endocrinol Diabetes Obes. 2007;14:306–310. doi: 10.1097/MED.0b013e3281e2c9fc

23. Bliss SP, Navratti AM, Xie J, Roberson MS. GnRH signaling, the gonadotrope and endocrine control of fertility. Front Neuroendocrinol. 2010 Jul;31(3):322-340.doi: 10.1016/j.yfrne.2010.04.002.

Smith JT, et al. Regulation of Kiss1 gene expression in the brain of the female mouse. Endocrinology. 2005;146:3686–3692. doi: 10.1210/en.2005-0488.

Zoeller RT, Seeburg PH, Young WS., III In situ hybridization histochemistry for messenger ribonucleic acid (mRNA) encoding gonadotropin-releasing hormone (GnRH): effect of estrogen on cellular levels of GnRH mRNA in female rat brain. Endocrinology. 1988;122:2570–2577. doi: 10.1210/endo-122-6-2570.

Petersen SL, Ottem EN, Carpenter CD. Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol. Biol Reprod. 2003;69:1771–1778. doi: 10.1095/biolreprod.103.019745.

Naftolin F, Garcia-Segura LM, Horvath TL, Zsarnovszky A, Demir N, Fadiel A, Leranth C, Vondracek-Klepper S, Lewis C, Chang A, Parducz A. Estrogen-induced hypothalamic synaptic plasticity and pituitary sensitization in the control of the estrogen-induced gonadotrophin surge. Reprod Sci. 2007;14:101–116. doi: 10.1177/1933719107301059.

Estrada KM, Clay CM, Pompolo S, Smith JT, Clarke IJ. Elevated KiSS-1 expression in the arcuate nucleus prior to the cyclic preovulatory gonadotrophin-releasing hormone/lutenising hormone surge in the ewe suggests a stimulatory role for kisspeptin in oestrogen-positive feedback. J Neuroendocrinol. 2006;18:806–809. doi: 10.1111/j.1365-2826.2006.01485.x.

Herbison AE. Estrogen positive feedback to gonadotropin-releasing hormone (GnRH) neurons in the rodent: the case for the rostral periventricular area of the third ventricle (RP3V) Brain Res Rev. 2008;57:277–287. doi: 10.1016/j.brainresrev.2007.05.006

Petersen SL, Ottem EN, Carpenter CD. Direct and indirect regulation of gonadotropin-releasing hormone neurons by estradiol. Biol Reprod. 2003 Dec;69(6):1771-8.doi: 10.1095/biolreprod.103.019745.

Simonian SX, Spratt DP, Herbison AE. Identification and characterization of estrogen receptor alpha-containing neurons projecting to the vicinity of the gonadotropin-releasing hormone perikarya in the rostral preoptic area of the rat. J Comp Neurol. 1999;411:346–358. doi: 10.1002/(sici)1096-9861(19990823)411:2<346::aid-cne13>3.0.co;2-s.

Demirol A, Bozdağ G, Gürgan T. GnRH Agonistleri Ve Antagonistleri: Güncel Yönleri. İnönü Üniversitesi Tıp Fakültesi Dergisi. 13(2) 135-140 (2006)

Cornea A, Janovick JA, Maya-Nunez G, Conn PM. Gonadotropin releasing hormone receptor microaggregation. Rate monitored by fluorescence resonance energy transfer. J Biol Chem. 2001;276(3):2153-2158. doi: 10.1074/jbc.M007850200. Epub 2000 Oct 16

Cornea A, Janovich JA, Lin X, Conn PM. Simultaneous and independent

visualization of the gonadotropin-releasing hormone receptor and

its ligand: evidence for independent processing and recycling in living cells. Endocrinology. 1999 September 140(9):4272-80. doi: 10.1210/endo.140.9.7049

Gordon K, Hodgen GD. GnRH agonists and antagonists in assisted reproduction. Balliere’s Clinical Obstet & Gynecol. 1992 Jun;6(2):247-65. doi: 10.1016/s0950-3552(05)80085-9

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