The site of the Media Sphera Publishers contains materials intended solely for healthcare professionals.
By closing this message, you confirm that you are a certified medical professional or a student of a medical educational institution.

Maiborodin I.V.

Knorre Institute of Chemical Biology and Fundamental Medicine The Russian Academy of Sciences, Novosibirsk, Russia

Sheplev B.V.

Novosibirsk Medical and Dental Institute “Dentmaster”, Novosibirsk, Russia

Chernomortseva E.S.

Immanuel Kant Baltic Federal University, Kaliningrad, Russia

Interaction of gonadotropin-releasing hormone with the gastrointestinal tract: experimental and clinical perspectives

Authors:

Maiborodin I.V., Sheplev B.V., Chernomortseva E.S.

More about the authors

Read: 440 times


To cite this article:

Maiborodin IV, Sheplev BV, Chernomortseva ES. Interaction of gonadotropin-releasing hormone with the gastrointestinal tract: experimental and clinical perspectives. Russian Journal of Evidence-Based Gastroenterology. 2026;15(2):43‑52. (In Russ.)
https://doi.org/10.17116/dokgastro20261502143

Recommended articles:
Modern approaches to a colon poly­posis early dete­ction. Russian Journal of Preventive Medi­cine. 2025;(7):91-93
Hepa­tic hema­ngioma: what surgeons need to know. Piro­gov Russian Journal of Surgery. 2025;(11):102-108
Role of gut microbiota in aging processes. Piro­gov Russian Journal of Surgery. 2025;(11-2):67-73
Cefo­perazone/sulbactam-induced coagulopathy following pancreatic surgery. Piro­gov Russian Journal of Surgery. 2026;(6):98-103

References:

  1. Maiborodin IV, Pichigina AK, Maiborodina VI, Lushnikova EL. Physiological Aspects of the Application of Gonadotropin-Releasing Hormone Agonists in Obstetric-Gynecological Clinic and Experiment. Rossijskij fiziologicheskij zhurnal im. IM. Sechenova. 2022;58(6):1865-1878. (In Russ.). https://doi.org/10.1134/S0022093022060163
  2. Maiborodin IV, Sheplev BV. Andrological aspects of the effects of gonadotropin-releasing hormone agonists in experiment and clinic. Acta Biomedica Scientifica. 2024;9(6):85-99. (In Russ.). https://doi.org/10.29413/ABS.2024-9.6.9
  3. Maiborodin IV, Marinkin IO, Onoprienko NV, Maiborodina VI. Gonadotropin-Releasing Hormone and Organs of the Immune System. Rossijskij fiziologicheskij zhurnal im. IM. Sechenova. 2024;60(4):1504-1515. (In Russ.). https://doi.org/10.1134/S0022093024040197
  4. Ladisa C, Ma Y, Habibi HR. Metabolic Changes During Growth and Reproductive Phases in the Liver of Female Goldfish (Carassius auratus). Frontiers in Cell and Developmental Biology. 2022;10:834688. https://doi.org/10.3389/fcell.2022.834688
  5. González-Martínez D, Sarasquete C, Pascual E, Muñoz-Cueto JA. Expression of gonadotrophin-releasing hormone binding sites in somatic tissues of the gilthead seabream (Sparus aurata): a quantitative autoradiographic study. Histology and Histopathology. 2006;21(10):1065-1073. https://doi.org/10.14670/HH-21.1065
  6. Wang L, Cao H, Jiang N, Zhang N, Zhang J, Hou R, Chen C, Wang Y, Li X, Li D, Ji Q. Differential expression of gonadotropin-releasing hormone (GnRH) in pancreas during rat pregnancy. Endocrine. 2009;36(3):538-545.  https://doi.org/10.1007/s12020-009-9264-1
  7. Chen L, Yin SD, Sun XD.  EffectsofGnRH-Ianalogoninositol1,4,5-triphosphate(IP(3))ingastricparietalcellsofratsinvitro].Xibaoyufenzimianyixuezazhi=ChineseJournalofCellularandMolecularImmunology.2009;25(2):111-114.
  8. Aguilar-Rojas A, Huerta-Reyes M. Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review). Oncology Reports. 2009;22(5):981-990.  https://doi.org/10.3892/or_00000525
  9. Chu C, Xu B, Huang W. A study on expression of FSH and its effects on the secretion of insulin and glucagon in rat pancreas. Tissue and Cell. 2010;42(6):370-375.  https://doi.org/10.1016/j.tice.2010.09.001
  10. Hammar O, Veress B, Montgomery A, Ohlsson B. Expression of Luteinizing Hormone Receptor in the Gastrointestinal Tract in Patients with and without Dysmotility. Drug Target Insights. 2012;6:13-18.  https://doi.org/10.33393/dti.2012.2403
  11. Sand E, Voss U, Ohlsson B, Ekblad E. Luteinizing hormone receptors are expressed in rat myenteric neurons and mediate neuronal loss. Autonomic Neuroscience. 2015;193:104-107.  https://doi.org/10.1016/j.autneu.2015.10.001
  12. Zoghi M, Jalilian AR, Niazi A, Johari-Daha F, Alirezapour B, Ramezanpour S. Development of a (68)Ga-peptide tracer for PET GnRH1-imaging. Annals of Nuclear Medicine. 2016; 30(6):400-408.  https://doi.org/10.1007/s12149-016-1074-y
  13. Cao N, Cao L, Gao M, Wang H, Zhang L, Yang L. Changes in mRNA and protein levels of gonadotropin releasing hormone and receptor in ovine thymus, lymph node, spleen, and liver during early pregnancy. Domestic Animal Endocrinology. 2021;76:106607. https://doi.org/10.1016/j.domaniend.2021.106607
  14. Fanis P, Neocleous V, Papapetrou I, Phylactou LA, Skordis N. Gonadotropin-Releasing Hormone Receptor (GnRHR) and Hypogonadotropic Hypogonadism. International Journal of Molecular Sciences. 2023;24(21):15965. https://doi.org/10.3390/ijms242115965
  15. Patel B, Koysombat K, Mills EG, Tsoutsouki J, Comninos AN, Abbara A, Dhillo WS. The Emerging Therapeutic Potential of Kisspeptin and Neurokinin B. Endocrine Reviews. 2024;45(1):30-68.  https://doi.org/10.1210/endrev/bnad023
  16. Jyrkäs J, Tolonen A. Hepatic in vitro metabolism of peptides; Comparison of human liver S9, hepatocytes and Upcyte hepatocytes with cyclosporine A, leuprorelin, desmopressin and cetrorelix as model compounds. Journal of Pharmaceutical and Biomedical Analysis. 2021;196:113921. https://doi.org/10.1016/j.jpba.2021.113921
  17. Li H, Zhang G, Guo Y, Deng J, Fischer H, Craig LB, Kem DC, Yu X. Autoimmune activation of the GnRH receptor induces insulin resistance independent of obesity in a female rat model. Physiological Reports. 2021;8(24):e14672. https://doi.org/10.14814/phy2.14672
  18. Liu X, Zhu L, Ma J, Qiao X, Zhu D, Liu L, Leng X. Target-specific delivery of siRNA into hepatoma cells’ cytoplasm by bifunctional carrier peptide. Drug Delivery and Translational Research. 2017;7(1):147-155.  https://doi.org/10.1007/s13346-016-0348-1
  19. Eluu SC, Obayemi JD, Salifu AA, Yiporo D, Oko AO, Aina T, Oparah JC, Ezeala CC, Etinosa PO, Ugwu CM, Esimone CO, Soboyejo WO. In-vivo studies of targeted and localized cancer drug release from microporous poly-di-methyl-siloxane (PDMS) devices for the treatment of triple negative breast cancer. Scientific Reports. 2024;14(1):31.  https://doi.org/10.1038/s41598-023-50656-6
  20. Kyritsi K, Meng F, Zhou T, Wu N, Venter J, Francis H, Kennedy L, Onori P, Franchitto A, Bernuzzi F, Invernizzi P, McDaniel K, Mancinelli R, Alvaro D, Gaudio E, Alpini G, Glaser S. Knockdown of Hepatic Gonadotropin-Releasing Hormone by Vivo-Morpholino Decreases Liver Fibrosis in Multidrug Resistance Gene 2 Knockout Mice by Down-Regulation of miR-200b. American Journal of Pathology. 2017;187(7):1551-1565. https://doi.org/10.1016/j.ajpath.2017.03.013
  21. Hua L, Feng B, Huang L, Li J, Luo T, Jiang X, Han X, Che L, Xu S, Lin Y, Fang Z, Wu D, Zhuo Y. Time-restricted feeding improves the reproductive function of female mice via liver fibroblast growth factor 21. Clinical and Translational Medicine. 2020;10(6):e195. https://doi.org/10.1002/ctm2.195
  22. Klenke U, Taylor-Burds C, Wray S. Metabolic influences on reproduction: adiponectin attenuates GnRH neuronal activity in female mice. Endocrinology. 2014;155(5):1851-1863. https://doi.org/10.1210/en.2013-1677
  23. Yang G, Song Q, Sun C, Qin J, Jia J, Yuan X, Zhang Y, Li W. Ctrp9 and adiponectin receptors in Nile tilapia (Oreochromis niloticus): Molecular cloning, tissue distribution and effects on reproductive genes. General and Comparative Endocrinology. 2018;265:160-173.  https://doi.org/10.1016/j.ygcen.2018.05.033
  24. McMillin M, Frampton G, Quinn M, Divan A, Grant S, Patel N, Newell-Rogers K, DeMorrow S. Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling. Molecular Endocrinology. 2015;29(12):1720-1730. https://doi.org/10.1210/me.2015-1087
  25. Aapkes SE, Bernts LHP, van den Berg AP, van den Berg M, Blokzijl H, Cantineau AEP, van Gastel MDA, de Haas RJ, Kappert P, Müller RU, Nevens F, Torra R, Visser A, Drenth JPH, Gansevoort RT. Protocol for a randomized controlled multicenter trial assessing the efficacy of leuprorelin for severe polycystic liver disease: the AGAINST-PLD study. BMC Gastroenterology. 2022;22(1):82.  https://doi.org/10.1186/s12876-022-02142-y
  26. Zhong H, Hu J, Zhou Y. Transcriptomic evidence of luteinizing hormone-releasing hormone agonist (LHRH-A) regulation on lipid metabolism in grass carp (Ctenopharyngodon idella). Genomics. 2021;113(1 Pt 2):1265-1271. https://doi.org/10.1016/j.ygeno.2020.09.043
  27. Gild P, Cole AP, Krasnova A, Dickerman BA, von Landenberg N, Sun M, Mucci LA, Lipsitz SR, Chun FK, Nguyen PL, Kibel AS, Choueiri TK, Basaria S, Trinh QD. Liver Disease in Men Undergoing Androgen Deprivation Therapy for Prostate Cancer. The Journal of Urology. 2018;200(3):573-581.  https://doi.org/10.1016/j.juro.2018.03.135
  28. Sawazaki H, Kitamura Y, Yagi K, Arai Y. Impact of Androgen Deprivation Therapy on Non-Alcoholic Fatty Liver Disease in Patients with Prostate Cancer: A CT Evaluation. Urologia Internationalis. 2020;104(5-6):425-430.  https://doi.org/10.1159/000507351
  29. Fushimi C, Tada Y, Takahashi H, Nagao T, Ojiri H, Masubuchi T, Matsuki T, Miura K, Kawakita D, Hirai H, Hoshino E, Kamata S, Saotome T. A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma. Annals of Oncology. 2018;29(4):979-984.  https://doi.org/10.1093/annonc/mdx771
  30. Valentine A, Davis S, Furniss A, Dowshen N, Kazak AE, Lewis C, Loeb DF, Nahata L, Pyle L, Schilling LM, Sequeira GM, Nokoff N. Multicenter Analysis of Cardiometabolic-related Diagnoses in Transgender and Gender-Diverse Youth: A PEDSnet Study. The Journal of Clinical Endocrinology and Metabolism. 2022;107(10):e4004-e4014. https://doi.org/10.1210/clinem/dgac469
  31. Sasaki Y, Kajino H, Gotoda H. A Case of Nonalcoholic Steatohepatitis in Central Precocious Puberty Aggravated by Gonadotropin-releasing Hormone Analog. JPGN Reports. 2020;1(2):e014. https://doi.org/10.1097/PG9.0000000000000014
  32. Kasaven LS, Goumenou A, Adegoke K. Multiorgan failure associated with severe ovarian hyperstimulation syndrome due to inadequate protocol optimisation: a rare but avoidable complication. BMJ Case Reports. 2018;2018:bcr2017223418. https://doi.org/10.1136/bcr-2017-223418
  33. Schagen SE, Cohen-Kettenis PT, Delemarre-van de Waal HA, Hannema SE. Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents. The Journal of Sexual Medicine. 2016;13(7):1125-1132. https://doi.org/10.1016/j.jsxm.2016.05.004
  34. Tebbens M, Schutte M, Troelstra MA, Bruinstroop E, de Mutsert R, Nederveen AJ, den Heijer M, Bisschop PH. Sex Steroids Regulate Liver Fat Content and Body Fat Distribution in Both Men and Women: A Study in Transgender Persons. Journal of Clinical Endocrinology and Metabolism. 2023;109(1):e280-e290. https://doi.org/10.1210/clinem/dgad409
  35. Yoon EL, Yuk JS. Use of Ulipristal Acetate and Risk of Liver Disease: A Nationwide Cohort Study. The Journal of Clinical Endocrinology and Metabolism. 2021;106(6):1773-1782. https://doi.org/10.1210/clinem/dgab081
  36. Alshehre SM, Duffy S, Jones G, Ledger WL, Metwally M. A prospective, single-centre, single-arm, open label study of the long term use of a gonadotropin releasing hormone agonist (Triptorelin SR, 11.25 mg) in combination with Tibolone add-back therapy in the management of chronic cyclical pelvic pain. Reproductive Biology and Endocrinology. 2020;18(1):28.  https://doi.org/10.1186/s12958-020-00586-z
  37. Taché Y, Vale W, Rivier J, Brown M. Brain regulation of gastric secretion: influence of neuropeptides. Proceedings of the National Academy of Sciences of the United States of America. 1980;77(9):5515-5519. https://doi.org/10.1073/pnas.77.9.5515
  38. Soldani G, Del Tacca M, Bambini G, Polloni A, Bernardini C, Martinotti E, Martino E. Effects of gonadotropin-releasing hormone (GnRH) on gastric secretion and gastrin release in the dog. Journal of Endocrinological Investigation. 1982;5(6):393-396.  https://doi.org/10.1007/BF03350539
  39. Nakane T, Kanie N, Audhya T, Hollander CS. The effects of centrally administered neuropeptides on the development of gastric lesions in the rat. Life Sciences. 1985;36(12):1197-1203. https://doi.org/10.1016/0024-3205(85)90238-3
  40. Gama P, Alvares EP. Localization of luteinizing-hormone releasing hormone binding sites in the gastric mucosa of suckling rats. Anatomical Record. 2001;264(1):43-50.  https://doi.org/10.1002/ar.1123
  41. Motta G, Allasia S, Ghigo E, Lanfranco F. Ghrelin Actions on Somatotropic and Gonadotropic Function in Humans. Progress in Molecular Biology and Translational Science. 2016;138:3-25.  https://doi.org/10.1016/bs.pmbts.2015.11.001
  42. Imaki T, Yamada S, Harada S, Tsuchiya M, Sano T, Demura H. Amelioration of acromegaly after pituitary infarction due to gastrointestinal hemorrhage from gastric ulcer. Endocrine Journal. 1999;46(1):147-151.  https://doi.org/10.1507/endocrj.46.147
  43. Jyrkäs J, Lassila T, Tolonen A. Extrahepatic in vitro metabolism of peptides; comparison of human kidney and intestinal S9 fraction, human plasma and proximal tubule cells, using cyclosporine A, leuprorelin, and cetrorelix as model compounds. Journal of pharmaceutical and Biomedical Analysis. 2023;225:115219. https://doi.org/10.1016/j.jpba.2022.115219
  44. Jönsson A, Sand E, Ekblad E, Ohlsson B. Long-term follow-up of buserelin-induced enteric neuropathy in rats. Molecular Medicine Reports. 2016;13(4):3507-3513. https://doi.org/10.3892/mmr.2016.4968
  45. Ohlsson B, Ekblad E, Veress B, Montgomery A, Janciauskiene S. Antibodies against gonadotropin-releasing hormone (GnRH) and destruction of enteric neurons in 3 patients suffering from gastrointestinal dysfunction. BMC Gastroenterology. 2010;10:48.  https://doi.org/10.1186/1471-230X-10-48
  46. Janakiram NB, Mohammed A, Brewer M, Bryant T, Biddick L, Lightfoot S, Pathuri G, Gali H, Rao CV. Raloxifene and antiestrogenic gonadorelin inhibits intestinal tumorigenesis by modulating immune cells and decreasing stem-like cells. Cancer Prevention Research. 2014;7(3):300-309.  https://doi.org/10.1158/1940-6207.CAPR-13-0345
  47. Mangoni M, Sottili M, Gerini C, Fucci R, Pini A, Calosi L, Bonomo P, Detti B, Greto D, Meattini I, Simontacchi G, Loi M, Scartoni D, Furfaro I, Pallotta S, Livi L. Protective Effect of Leuprorelin on Radiation-induced Intestinal Toxicity. Anticancer Research. 2015;35(7):3875-3884.
  48. Wu D, Wang C, Simujide H, Liu B, Chen Z, Zhao P, Huangfu M, Liu J, Gao X, Wu Y, Li X, Chen H, Chen A. Reproductive Hormones Mediate Intestinal Microbiota Shifts during Estrus Synchronization in Grazing Simmental Cows. Animals (Basel). 2022;12(14):1751. https://doi.org/10.3390/ani12141751
  49. Mikołajczyk A, Złotkowska D. Subclinical Lipopolysaccharide from Salmonella Enteritidis Induces Dysregulation of Bioactive Substances from Selected Brain Sections and Glands of Neuroendocrine Axes. Toxins (Basel). 2019;11(2):91.  https://doi.org/10.3390/toxins11020091
  50. Wang L, Xu H, Tan B, Yi Q, Liu H, Deng H, Chen Y, Wang R, Tian J, Zhu J. Gut microbiota and its derived SCFAs regulate the HPGA to reverse obesity-induced precocious puberty in female rats. Frontiers in Endocrinology. 2022;13:1051797. https://doi.org/10.3389/fendo.2022.1051797
  51. Wang Y, Du W, Lei K, Wang B, Wang Y, Zhou Y, Li W. Effects of Dietary Bacillus licheniformis on Gut Physical Barrier, Immunity, and Reproductive Hormones of Laying Hens. Probiotics and Antimicrobial Proteins. 2017;9(3):292-299.  https://doi.org/10.1007/s12602-017-9252-3
  52. Ho JS, Nagle GT, Mathias JR, Clench MH, Fan X, Kalmaz GD, Sallustio JE, Eaker EY. Presence of gonadotropin-releasing hormone (GnRH) receptor mRNA in rat myenteric plexus cells. Comparative Biochemistry and Physiology. 1996;113(4):817-821.  https://doi.org/10.1016/0305-0491(95)02114-0
  53. Hammar O, Ohlsson B, Veress B, Alm R, Fredrikson GN, Montgomery A. Depletion of enteric gonadotropin-releasing hormone is found in a few patients suffering from severe gastrointestinal dysmotility. Scandinavian Journal of Gastroenterology. 2012;47(10):1165-1173. https://doi.org/10.3109/00365521.2012.706826
  54. Kapuvári B, Hegedüs R, Schulcz Á, Manea M, Tóvári J, Gacs A, Vincze B, Mező G. Improved in vivo antitumor effect of a daunorubicin — GnRH-III bioconjugate modified by apoptosis inducing agent butyric acid on colorectal carcinoma bearing mice. Investigational New Drugs. 2016;34(4):416-423.  https://doi.org/10.1007/s10637-016-0354-7
  55. Inaba M, Otani Y, Nishimura K, Takaha N, Okuyama A, Koga M, Azuma J, Kawase I, Kasayama S. Marked hyperglycemia after androgen-deprivation therapy for prostate cancer and usefulness of pioglitazone for its treatment. Metabolism. 2005;54(1):55-59.  https://doi.org/10.1016/j.metabol.2004.07.010
  56. Mansano NDS, Paradela RS, Bohlen TM, Zanardi IM, Chaves FM, Silveira MA, Tavares MR, Donato J Jr, Frazao R. Vasoactive intestinal peptide exerts an excitatory effect on hypothalamic kisspeptin neurons during estrogen negative feedback. Molecular and Cellular Endocrinology. 2022;542:111532. https://doi.org/10.1016/j.mce.2021.111532
  57. Tanaka S, Zmora N, Levavi-Sivan B, Zohar Y. Vasoactive Intestinal Peptide Indirectly Elicits Pituitary LH Secretion Independent of GnRH in Female Zebrafish. Endocrinology. 2022;163(2):bqab264. https://doi.org/10.1210/endocr/bqab264
  58. Piet R, Dunckley H, Lee K, Herbison AE. Vasoactive Intestinal Peptide Excites GnRH Neurons in Male and Female Mice. Endocrinology. 2016;157(9):3621-3630. https://doi.org/10.1210/en.2016-1399
  59. Kauffman AS, Sun Y, Kim J, Khan AR, Shu J, Neal-Perry G. Vasoactive intestinal peptide modulation of the steroid-induced LH surge involves kisspeptin signaling in young but not in middle-aged female rats. Endocrinology. 2014;155(6):2222-2232. https://doi.org/10.1210/en.2013-1793
  60. Murányi J, Varga A, Gurbi B, Gyulavári P, Mező G, Vántus T. In Vitro Imaging and Quantification of the Drug Targeting Efficiency of Fluorescently Labeled GnRH Analogues. Journal of Visualized Experiments. 2017;(121):55529. https://doi.org/10.3791/55529

Email Confirmation

An email was sent to test@gmail.com with a confirmation link. Follow the link from the letter to complete the registration on the site.

Email Confirmation

We use cооkies to improve the performance of the site. By staying on our site, you agree to the terms of use of cооkies. To view our Privacy and Cookie Policy, please. click here.