Skip to main content
SpringerLink
Log in

Salmon GnRH and Its Analogues Bind the Human Placental Receptor

  • Original Article
  • Published:
The Journal of the Society for Gynecologic Investigation: JSGI Aims and scope Submit manuscript

Abstract

Objective

The presence of GnRH receptors in the human placenta has been recognized for a number of years. However, mammalian GnRH, which is expressed in placental tissues, has limited affinity for the chorionic receptor. On the basis of immunological and bioactivity data, we have previously proposed that the chorionic GnRH may differ from mammalian GnRH.

Results

Using our receptor assay method with the labeled mammalian GnRH analogue Buserelin, salmon GnRH had a twofold greater affinity for the placental GnRH receptor than did mammalian GnRH and for the stable salmon GnRH analogue the affinity was increased tenfold. Using a homologous receptor assay method with a stable salmon GnRH analogue as label, the affinity for this salmon GnRH analogue had a Kd of 101 nmol/L.

Conclusion

The presence of these higher affinity receptors for non-mammalian GnRH in the human placenta has led us to propose that the chorionic tissues may express more than one isoform of GnRH and that non-mammalian GnRH, such as salmon GnRH, may be potent regulators of a placental functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Siler-Khodr TM, Khodr GS. Luteinizing hormone releasing factor content of the human placenta. Am J Obstet Gynecol 1978; 130:216–9.

    Article  CAS  PubMed  Google Scholar 

  2. Khodr GS, Siler-Khodr TM. Localization of luteinizing hormone releasing factor (LRF) in the human placenta. Fertil Steril 1978;29:523–6.

    Article  CAS  PubMed  Google Scholar 

  3. Siler-Khodr TM, Khodr GS. Extrahypothalamic luteinizing hormone releasing factor (LRF): Release of immunoreactive LRF by the human placenta in vitro. Fertil Steril 1979;22:294–6.

    Article  Google Scholar 

  4. Khodr GS, Siler-Khodr TM. Placental LRF and its synthesis. Science 1980;207:315–7.

    Article  CAS  PubMed  Google Scholar 

  5. Siler-Khodr TM, Khodr GS, Vickery BH, Nestor JJ Jr. Inhibition of hCG, alpha hCG and progesterone release from human placental tissue in vitro by a GnRH antagonist. Life Sci 1983;32: 2741–5.

    Article  CAS  PubMed  Google Scholar 

  6. Siler-Khodr TM, Khodr GS. Dose response analysis of GnRH stimulation of hCG release from human term placenta. Biol Reprod 1981;25:353–8.

    Article  CAS  PubMed  Google Scholar 

  7. Khodr GS, Siler-Khodr TM. The effect of luteinizing hormone releasing factor (LRF) on hCG secretion. Fertil Steril 1979;30: 301–4.

    Article  Google Scholar 

  8. Siler-Khodr TM, Khodr GS, Valenzuela G, Rhode J. Gonadotropin-releasing hormone effects on placental hormones during gestation: I. Alpha-human chorionic gonadotropin, human chorionic gonadotropin and human chorionic somatomammotropin. Biol Reprod 1986;34:245–54.

    Article  CAS  PubMed  Google Scholar 

  9. Siler-Khodr TM, Khodr GS, Valenzuela G, Rhode J. Gonadotropin-releasing hormone effects on placental hormones during gestation: II. Progesterone, estrone, estradiol and estriol. Biol Reprod 1986;34:255–64.

    Article  CAS  PubMed  Google Scholar 

  10. Siler-Khodr TM, Khodr GS, Valenzuela G, Harper Mj, Rhode J. GnRH effects on placental hormones during gestati. III. Prostaglandin E, prostaglandin F, and 13, 14-dihydro-15-ketoprostaglandin F. Biol Reprod 1986;35:312–9.

    Article  CAS  PubMed  Google Scholar 

  11. Petraglia F, Vaughan J, Vale W. Steroid hormones modulate the release of immunoreactive gonadotropin-releasing hormone from cultured human placental cells. J Clin Endocrinol Metab 1990;70:1173–8.

    Article  CAS  PubMed  Google Scholar 

  12. Iwashita M, Watanabe M, Adachi T, et al. Effect of gonadal steroids on gonadotropin-releasing hormones stimulated human chorionic gonadotropin release by trophoblast cells. Placenta 1989;10:103–12.

    Article  CAS  PubMed  Google Scholar 

  13. Siler-Khodr TM. Hypothalamic-like releasing hormones of the placenta. Clin Perinatol 1983;10:553–66.

    Article  CAS  PubMed  Google Scholar 

  14. Petraglia F, Vaughan J, Vale W. Inhibin and activin modulate the release of gonadotropin-releasing hormone, human chorionic gonadotropin, and progesterone from cultured human placental cells. Proc Natl Acad Sci USA 1991;86:5114–7.

    Article  Google Scholar 

  15. Cemerikic B, Maulik D, Ahmed MS. Opioids regulation of hCG release from trophoblast tissue is mediated by LHRH. Placenta 1992;13:9A (abstract).

    Article  Google Scholar 

  16. Petraglia F, Lim AT, Vale W. Adenosine 3′,5′-monophosphate, prostaglandins, and epinephrine stimulate the secretion of immunoreactive gonadotropin-releasing hormone from cultured human placental cells. J Clin Endocrinol Metab 1987;65:1020–5.

    Article  CAS  PubMed  Google Scholar 

  17. Barnea ER, Feldman D, Kaplan M. The effect of progesterone upon first trimester trophoblastic cell differentiation and human chorionic gonadotrophin secretion. Hum Reprod 1991;6:905–9.

    Article  CAS  PubMed  Google Scholar 

  18. Barnea ER, Kaplan M. Spontaneous, gonadotropin-releasing hormone-induced, and progesterone-inhibited pulsatile secretion of human chorionic gonadotropin in the first trimester placenta in vitro. J Clin Endocrinol Metab 1989;69:215–7.

    Article  CAS  PubMed  Google Scholar 

  19. Radovick S, Wondisford FE, Nakayama Y, Yamada M, Cutler GB Jr, Weintraub BD. Isolation and characterization of the human gonadotropin-releaing hormone gene in the hypothalamus and placenta. Mol Endocrinol 1990;4:476–80.

    Article  CAS  PubMed  Google Scholar 

  20. Adelman JP, Mason AJ, Hayflick JS, Seeburg PH. Isolation of the gene and hypothalamic cDNA for the common precursor of gonadotropin-releasing hormone and prolactin release-inhibiting factor in human and rat. Proc Natl Acad Sci USA 1986;83.179–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Duello TM, Tsai SJ, Van Ess PJ. In situ demonstration and characterization of progonadotropin-releasing hormone messenger ribonucleic acid in first trimester human placentas. Endocrinology 1993;133:2617–23.

    Article  CAS  PubMed  Google Scholar 

  22. Kelly AC, Rodgers A, Dong KW, Barrezueta NX, Blum M, Roberts JL. Gonadotropin-releasing hormone and chorionic gonadotropin gene expression in human placental development. DNA Cell Biol 1991;10:411–21.

    Article  CAS  PubMed  Google Scholar 

  23. Dong KW, Yu KL, Roberts JL. Identification of a major upstream transcription start site for the human progonadotropin-releasing hormone gene used in reproductive tissues and cell lines. Mol Endocrinol 1993;7:1654–66.

    CAS  PubMed  Google Scholar 

  24. Dong KW, Chen ZG, Cheng KW, Yu KL. Evidence for estrogen receptor-mediated regulation of human gonadotropin-releasing hormone promoter activity in human placental cells. Mol Cell Endocrinol 1996;117:241–6.

    Article  CAS  PubMed  Google Scholar 

  25. Currie A, Fraser H, Sharpe R. Human placental receptors for luteinizing hormone releasing hormone. Biochem Biophys Res Commun 1981;99:332–8.

    Article  CAS  PubMed  Google Scholar 

  26. Iwashita M, Evans MI, Catt KJ. Characterization of a gonadotropin-releasing hormone receptor site in term placenta and chorionic villi. J Clin Endocrinol Metab 1986;62:127–33.

    Article  CAS  PubMed  Google Scholar 

  27. Belisle S, Lehoux J, Bellabarba D, Gallo-Payet N, Guevin J. Dynamics of LHRH binding to human term placental cells from normal and anencephalic gestations. Mol Cell Endocrinol 1987; 49:195–202.

    Article  CAS  PubMed  Google Scholar 

  28. Bramley TA, McPhie CA, Menzies GS. Human placental gonadotrophin-releasing hormone (GnRH) binding sites: I. Characterization, properties and ligand specificity. Placenta 1992;13: 555–81.

    Article  CAS  PubMed  Google Scholar 

  29. Lin LS, Roberts VJ, Yen SS. Expression of human gonadotropin-releasing hormone receptor gene in the placenta and its functional relationship to human chorionic gonadotropin secretion. J Clin Endocrinol Metab 1997;80:580–5.

    Google Scholar 

  30. Boyle TA, Belt-Davis DI, Duello TM. Nucleotide sequence analyses predict that human pituitary and human placental gonadotropin-releasing hormone receptors have identical primary structures. Endocrine 1998;9:281–7.

    Article  CAS  PubMed  Google Scholar 

  31. Wolfahrt S, Kleine B, Rossmanith WG. Detection of gonadotrophin releasing hormone and its receptor mRNA in human placental trophoblasts using in-situ reverse transcription-polymerase chain reaction. Mol Hum Reprod 2000;4:999–1006.

    Article  Google Scholar 

  32. Cheng KW, Nathwani PS, Leung PCK. Regulation of human gonadotropin-releasing hormone receptor gene expression in placental cells. Endocrinology 2000;141:2340–9.

    Article  CAS  PubMed  Google Scholar 

  33. Petraglia F, Genazzani AD, Aguzzoli L, et al. Pulsatile fluctuations of plasma-gonadotropin-releasing hormone and corticotropin-releasing factor levels in healthy pregnant women. Acta Obstet Gynecol Scand 1994;73:284–9.

    Article  CAS  PubMed  Google Scholar 

  34. Seshagiri PB, Terasawa E, Hearn JP. The secretion of gonadotrophin-releasing hormone by peri-implantation embryos of the rhesus monkey: Comparison with the secretion of chorionic gonadotrophin. Hum Reprod 1994;9:1300–7.

    Article  CAS  PubMed  Google Scholar 

  35. Siler-Khodr TM, Kuehl TJ, Vickery BH. Effects of a gonadotropin-releasing hormone antagonist on hormonal levels in the pregnant baboon and on fetal outcome. Fertil Steril 1984;41: 448–54.

    Article  CAS  PubMed  Google Scholar 

  36. Kang IS, Kuehl TJ, Siler-Khodr TM. Effect of treatment with gonadotropin-releasing hormone analogues on pregnancy outcome in the baboon. Fertil Steril 1989;52:846–53.

    Article  CAS  PubMed  Google Scholar 

  37. Gupta SK, Singh M. Characteristics and bioefficacy of monoclonal antigonadotropin releasing hormone antibody. Am J Reprod Immunol Microbiol 1985;7:104–8.

    Article  CAS  PubMed  Google Scholar 

  38. Das C, Gupta SK, Talwar GP. Pregnancy interfering action of LHRH and anti-LHRH. J Steroid Biochem 1985;23:803–6.

    Article  CAS  PubMed  Google Scholar 

  39. Hodges JK, Hearn JP. Effects of immunisation against luteinising hormone releasing hormone on reproduction of the marmoset monkey Callithrix jacchus. Nature 1977;265:746–8.

    Article  CAS  PubMed  Google Scholar 

  40. Das C, Talwar GP. Pregnancy-terminating action of a luteinizing hormone-releasing hormone agonist D-Ser(But)6desGly10ProEA in baboons. Fertil Steril 1983;39:218–23.

    Article  CAS  PubMed  Google Scholar 

  41. Rao A, Moudgal N. Effect of LHRH injection on serum chorionic gonadotropin levels in the pregnant bonnet monkey (Macaca radiata). Obstet Gynecol 1984;12:1105–6.

    CAS  Google Scholar 

  42. Rao AJ, Chakraborti R, Kotagi SG, Ravindranath N, Moudgal NR. Effect of LHRH agonists and antagonists in male and female bonnet monkevs (Macaca radiata). J Steroid Biochem 1985;23: 807–9.

    Article  CAS  Google Scholar 

  43. Gautron JP, Pattou E, Kordon C. Occurrence of higher molecular forms of LHRH in fractionated extracts from rat hypothalamus, cortex and placenta. Mol Cell Endocrinol 1981;24:1–15.

    Article  CAS  PubMed  Google Scholar 

  44. Kang IS, Koong MK, Forman JS, Siler-Khodr TM. Dose-related action of gonadotropin-releasing hormone on basal prostanoid production from the human term placenta. Am J Obstet Gynecol 1991;165:1771–6.

    Article  CAS  PubMed  Google Scholar 

  45. King JA, Millar RP. Evolutionary aspects of gonadotropin-releasing hormone and its receptor. Cell Mol Neurobiol 1995;15: 5–23.

    Article  CAS  PubMed  Google Scholar 

  46. Dellovade TL, King JA, Millar RP, Rissman EF. Presence and differential distribution of distinct forms of immunoreactive gonadotropin-releasing hormone in the musk shrew brain. Neuroendocrinology 1993;58:166–77.

    Article  CAS  PubMed  Google Scholar 

  47. King JA, Steneveld AA, Curlewis JD, Rissman EF, Millar RP. Identification of chicken GnRH II in brains of metatherian and early-evolved eutherian species of mammals. Regul Pept 1994; 54:467–77.

    Article  CAS  PubMed  Google Scholar 

  48. Chen A, Yahalom D, Ben-Aroya N, Kaganovsky E, Okon E, Koch Y. A second isoform of gonadotropin-releasing hormone is present in the brain of human and rodents. FEBS Lett 2000;435: 199–203.

    Article  Google Scholar 

  49. White PJ3, Eisen JA, Kasten TL, Fernald RD. Second gene for gonadotropin-releasing hormone in humans. Med Sci 2000;95: 305–9.

    Google Scholar 

  50. Millar R, Conklin D, Lofton-Day C, et al. A novel human GnRH receptor homolog gene: Abundant and wide tissue distribution of the antisense transcript. J Endocrinol 1999;162:117–26.

    Article  CAS  PubMed  Google Scholar 

  51. Siler-Khodr TM, Grayson M. Action of chicken II GnRH on the human placenta. J Clin Endocrinol Metab 2001;86:804–10.

    CAS  PubMed  Google Scholar 

  52. Hunter W, Greenwood FC. Preparation of iodine–131-labelled human growth hormone of high specific activity. Nature 1962; 194:495–6.

    Article  CAS  PubMed  Google Scholar 

  53. Siler-Khodr TM, Kang IS, Jones MA, Harper MJK, Khodr GS, Rhode J. Characterization and purification of a placental protein that inactivates GnRH, TRH and angiotensin II. Placenta 1989; 10:285–96.

    Article  Google Scholar 

  54. Kang IS, Gallwitz J, Guzman V, Siler-Khodr TM. Definition of the enzyme kinetics and optimal activity of chorionic peptidase-1. The 23rd Annual Meeting of the Society for the Study of Reproduction (Vancouver) 1990;43,144 (Abstract 311).

  55. Kang IS, Siler-Khodr TM. Chorionic peptidase inactiviates GnRH as a post-proline peptidase. Placenta 1992;13:81–7.

    Article  CAS  PubMed  Google Scholar 

  56. Bramley TA, Menzies GS. Measurement of luteal and placental gonadotrophin-releasing hormone (GnRH) binding sites: Role of inactivation of GnRH tracer. Mol Hum Reprod 1996;2: 535–9.

    Article  CAS  PubMed  Google Scholar 

  57. Siler-Khodr TM, Grayson M, Fashaw S. Inhibition of chorionic peptidase-1 (Case-1) activity by analogues of GnRH. J Soc Gynecol Invest 1999;6,225A (abstract).

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics & Gynecology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, Room 416E, 78284, San Antonio, Texas, USA

    Theresa M. Siler-Khodr PhD & Marcia Grayson MA

Authors
  1. Theresa M. Siler-Khodr PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marcia Grayson MA
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Theresa M. Siler-Khodr PhD.

Additional information

These studies were supported by the CICCR Program of the CONRAD Program (CIG-98-18). Views expressed do not necessarily reflect those of CONRAD or CICCR.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siler-Khodr, T.M., Grayson, M. Salmon GnRH and Its Analogues Bind the Human Placental Receptor. Reprod. Sci. 8, 233–238 (2001). https://doi.org/10.1177/107155760100800408

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/107155760100800408

Key words

Search

Navigation