한국발생생물학회지:발생과생식 (Development and Reproduction)

  • 제28권1호
  • /
  • Pages.1-12
  • /
  • 2024
  • /
  • 2465-9525(pISSN)
  • /
  • 2465-9541(eISSN)
한국발생생물학회 (The Korean Society of Developmental Biology)
권호 표지
DOI QR코드

DOI QR Code

Gonadotropins Regulate the mRNA Expression of Gonadotropin-Releasing Hormone and Its Receptors in the Mouse Ovary and Uterus

  • Soeun Moon (Department of Bioenvironmental Technology, College of Sciences Technology Convergence, Seoul Women's University) ;
  • Bokyeong Yun (Department of Bioenvironmental Technology, College of Sciences Technology Convergence, Seoul Women's University) ;
  • Minju Lee (Department of Bioenvironmental Technology, College of Sciences Technology Convergence, Seoul Women's University) ;
  • Eunji Seok (Department of Biohealth Convergence, College of Sciences Technology Convergence, Seoul Women's University) ;
  • Jinah Ha (Department of Biohealth Convergence, College of Sciences Technology Convergence, Seoul Women's University) ;
  • Hyunwon Yang (Department of Biohealth Convergence, College of Sciences Technology Convergence, Seoul Women's University)
  • 투고 : 2023.12.08
  • 심사 : 2024.02.27
  • 발행 : 2024.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Gonadotropin-releasing hormone (GnRH), a critical hormone produced in the hypothalamus, is essential for regulating reproductive processes. It has also been demonstrated the presence of GnRH and its receptors (GnRHR) in ovarian and uterine tissues, but little was known about the regulation mechanism of their expression in these organs and ovarian aging. Therefore, the aim of this study was to investigate the expression of GnRHR in the ovary and uterus of mice, particularly after high-dose gonadotropin treatments and in relation to aging. Quantitative real-time-PCR (qRT-PCR) revealed that pituitary gland had the highest GnRHR expression in both young and aged mice. In addition, liver expression was higher in young mice, whereas thymus expression was higher in aged mice. GnRHR mRNA was present in the ovaries of both young and aged mice but nearly undetectable in the uterus of aged mice. We next examined the expression of GnRHR in the ovary and uterus in response to high-dose administration of pregnant mare serum gonadotropin (PMSG). After PMSG administration, GnRH mRNA levels were significantly decreased in the ovary but increased in the uterus. The expression of GnRH mRNA in these organs showed opposite trends to that of GnRHR expression. These results suggest the involvement of GnRH in age-related reproductive decline and the potential effects of high-dose gonadotropin treatments on reproductive organ function.

키워드

과제정보

This work was supported by a special research grant from Seoul Women's University (2024).

참고문헌

  1. Acevedo B, Gomez-Palomares JL, Ricciarelli E, Hernandez ER (2006) Triggering ovulation with gonadotropin-releasing hormone agonists does not compromise embryo implantation rates. Fertil Steril 86:1682-1687.
  2. Aguilar-Rojas A, Huerta-Reyes M (2009) Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells. Oncol Rep 22:981-990.
  3. Caligara C, Navarro J, Vargas G, Simon C, Pellicer A, Remohi J (2001) The effect of repeated controlled ovarian stimulation in donors. Hum Reprod 16:2320-2323.
  4. Cao N, Cao L, Gao M, Wang H, Zhang L, Yang L (2021) Changes in mRNA and protein levels of gonadotropin releasing hormone and receptor in ovine thymus, lymph node, spleen, and liver during early pregnancy. Domest Anim Endocrinol 76:106607.
  5. Catt KJ, Loumaye E, Wynn PC, Iwashita M, Hirota K, Morgan RO, Chang JP (1985) GnRH receptors and actions in the control of reproductive function. J Steroid Biochem 23:677-689.
  6. Cheung LWT, Wong AST (2008) Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues. FEBS J 275:5479-5495.
  7. Choi JH, Blake Gilks C, Auersperg N, Leung PCK (2006) Immunolocalization 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.
  8. Ciechanowska M, Lapot M, Mateusiak K, Przekop F (2010) Neuroendocrine regulation of GnRH release and expression of GnRH and GnRH receptor genes in the hypothalamus-pituitary unit in different physiological states. Reprod Biol 10:85-124.
  9. Clark ZL, Ruebel ML, Schall PZ, Karl KR, Ireland JJ, Latham KE (2022) Follicular hyperstimulation dysgenesis: New explanation for adverse effects of excessive FSH in ovarian stimulation. Endocrinology 163:bqac100.
  10. Deryabin PI, Borodkina AV (2023) Epigenetic clocks provide clues to the mystery of uterine ageing. Hum Reprod Update 29:259-271.
  11. Dong KW, Marcelin K, Hsu MI, Chiang CM, Hoffman G, Roberts JL (1998) Expression of gonadotropin-releasing hormone (GnRH) gene in human uterine endometrial tissue. Mol Hum Reprod 4:893-898.
  12. Elias AN, Wilson AF (1993) Exercise and gonadal function. Hum Reprod 8:1747-1761.
  13. Fraser HM, Sellar RE, Illingworth PJ, Eidne KA (1996) GnRH receptor mRNA expression by insitu hybridization in the primate pituitary and ovary. Mol Hum Reprod 2:117-121.
  14. Gong JG, Bramley TA, Gutierrez CG, Peters AR, Webb R (1995) Effects of chronic treatment with a gonadotrophin-releasing hormone agonist on peripheral concentrations of FSH and LH, and ovarian function in heifers. J Reprod Fertil 105:263-270.
  15. Guo S, Li Z, Yan L, Sun Y, Feng Y (2018) GnRH agonist improves pregnancy outcome in mice with induced adenomyosis by restoring endometrial receptivity. Drug Des Devel Ther 12:1621-1631.
  16. Hillensjo T, LeMaire WJ (1980) Gonadotropin releasing hormone agonists stimulate meiotic maturation of follicle-enclosed rat oocytes in vitro. Nature 287:145-146.
  17. Imai A, Takagi A, Horibe S, Takagi H, Tamaya T (1998) Evidence for tight coupling of gonadotropin-releasing hormone receptor to stimulated Fas ligand expression in reproductive tract tumors: Possible mechanism for hormonal control of apoptotic cell death. J Clin Endocrinol Metab 83:427-431.
  18. Jacobs HS, Agrawal R (1998) 4 Complications of ovarian stimulation. Bailliere's Clin Obstet Gynaecol 12:565-579.
  19. Kakar SS, Jennes L (1995) Expression of gonadotropin-releasing hormone and gonadotropin-releasing hormone receptor mRNAs in various non-reproductive human tissues. Cancer Lett 98:57-62.
  20. Knecht M, Ranta T, Feng P, Shinohara O, Catt K (1985) Gonadotropin-releasing hormone as a modulator of ovarian function. J Steroid Biochem 23:771-778.
  21. Li P, Zhu H, Tan L, Zhao D, Ma L, Xiang Y, Zhang D, Dou Q, Lu N (2015) Effects of high progesterone on outcomes of in vitro fertilization-embryo transfer in patients with different ovarian responses. Syst Biol Reprod Med 61:161-167.
  22. Maggi R, Cariboni AM, Marelli MM, Moretti RM, Andre V, Marzagalli M, Limonta P (2016) GnRH and GnRH receptors in the pathophysiology of the human female reproductive system. Hum Reprod Update 22:358-381.
  23. Melnikova VI, Lifantseva NV, Voronova SN, Zakharova LA (2019) Gonadotropin-releasing hormone in regulation of thymic development in rats: Profile of thymic cytokines. Int J Mol Sci 20:4033.
  24. Meresman GF, Bilotas MA, Lombardi E, Tesone M, Sueldo C, Baranao RI (2003) Effect of GnRH analogues on apoptosis and release of interleukin-1β and vascular endothelial growth factor in endometrial cell cultures from patients with endometriosis. Hum Reprod 18:1767-1771.
  25. Metallinou C, Asimakopoulos B, Schroer A, Nikolettos N (2007) Gonadotropin-releasing hormone in the ovary. Reprod Sci 14:737-749.
  26. Michael Conn P, Crowley WF Jr (1994) Gonadotropin-releasing hormone and its analogs. Annu Rev Med 45:391-405.
  27. Minaretzis D, Jakubowski M, Mortola JF, Pavlou SN (1995) Gonadotropin-releasing hormone receptor gene expression in human ovary and granulosa-lutein cells. J Clin Endocrinol Metab 80:430-434.
  28. Moghadam ARE, Moghadam MT, Hemadi M, Saki G (2022) Oocyte quality and aging. JBRA Assist Reprod 26:105-122.
  29. Nelson SM, Telfer EE, Anderson RA (2013) The ageing ovary and uterus: New biological insights. Hum Reprod Update 19:67-83.
  30. Nieschlag E, Simoni M, Gromoll J, Weinbauer GF (1999) Role of FSH in the regulation of spermatogenesis: Clinical aspects. Clin Endocrinol 51:139-146.
  31. Nyuji M, Yamamoto I, Hamada K, Kazeto Y, Okuzawa K (2019) Effect of GnRHa on plasma levels of Fsh and Lh in the female greater amberjack Seriola dumerili. J Fish Biol 95:1350-1354.
  32. Parborell F, Irusta G, Vitale A, Gonzalez O, Pecci A, Tesone M (2005) Gonadotropin-releasing hormone antagonist antide inhibits apoptosis of preovulatory follicle cells in rat ovary. Biol Reprod 72:659-666.
  33. Peng C, Fan NC, Ligier M, Vaananen J, Leung PC (1994) Expression and regulation of gonadotropin-releasing hormone (GnRH) and GnRH receptor messenger ribonucleic acids in human granulosa-luteal cells. Endocrinology 135:1740-1746.
  34. Pieper DR, Richards JS, Marshall JC (1981) Ovarian gonadotropin-releasing hormone (GnRH) receptors: Characterization, distribution, and induction by GnRH. Endocrinology 108:1148-1155.
  35. Raga F, Casan EM, Kruessel JS, Wen Y, Huang HY, Nezhat C, Polan ML (1998) Quantitative gonadotropin-releasing hormone gene expression and immunohistochemical localization in human endometrium throughout the menstrual cycle. Biol Reprod 59:661-669.
  36. Schafer-Somi S, Kowalewski MP, Kanca H, Bozkurt MF, Gram A, Sabitzer S, Kucukaslan I, Ay SS, Aslan S (2015) GnRH and its receptor (GnRH-R) are expressed in the canine placenta and uterus. Theriogenology 84:1482-1489.
  37. Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y, Redding TW, Nair RMG, Debeljuk L, White WF (1971) Gonadotropin-releasing hormone: One polypeptide regulates secretion of luteinizing and follicle-stimulating hormones. Science 173:1036-1038.
  38. Schirman-Hildesheim TD, Bar T, Ben-Aroya N, Koch Y (2005) Differential gonadotropin-releasing hormone (GnRH) and GnRH receptor messenger ribonucleic acid expression patterns in different tissues of the female rat across the estrous cycle. Endocrinology 146:3401-3408.
  39. Shirasuna K, Iwata H (2017) Effect of aging on the female reproductive function. Contracept Reprod Med 2:23.
  40. Singh P, Krishna A (2010) Effects of GnRH agonist treatment on steroidogenesis and folliculogenesis in the ovary of cyclic mice. J Ovarian Res 3:26.
  41. Smith MS (2009) Estrus and menstrual cycles: Neuroendocrine control. In: Squire LR (ed), Encyclopedia of Neuroscience. Elsevier, Amsterdam, Netherland, pp 1-5.
  42. Sonntag B, Kiesel L, Nieschlag E, Behre HM (2005) Differences in serum LH and FSH levels using depot or daily GnRH agonists in controlled ovarian stimulation: Influence on ovarian response and outcome of ART. J Assist Reprod Genet 22:277-283.
  43. Torrealday S, Lalioti MD, Guzeloglu-Kayisli O, Seli E (2013) Characterization of the gonadotropin releasing hormone receptor (GnRHR) expression and activity in the female mouse ovary. Endocrinology 154:3877-3887.
  44. Wang X, Wang L, Xiang W (2023) Mechanisms of ovarian aging in women: A review. J Ovarian Res 16:67.
  45. Whang J, Ahn C, Kim S, Seok E, Yang Y, Han G, Jo H, Yang H (2021) Effects of repeated ovarian stimulation on ovarian function and aging in mice. Dev Reprod 25:213-223.
  46. Wu Y, Li M, Zhang J, Wang S (2023) Unveiling uterine aging: Much more to learn. Ageing Res Rev 86:101879.