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.
1. Siler-Khodr TM, Khodr GS. Luteinizing hormone releasing factor content of the human placenta. Am J Obstet Gynecol1978;130:216-219.
2.
2. Khodr GS, Siler-Khodr TM. Localization of luteinizing hormone releasing factor (LRF) in the human placenta. Fertil Steril1978;29:523-526.
3.
3. Siler-Khodr TM, Khodr GS. Extrahypothalamic luteinizing hormone releasing factor (LRF): Release of immunoreactive LRF by the human placenta in vitro. Fertil Steril1979;22:294-296.
4.
4. Khodr GS, Siler-Khodr TM. Placental LRF and its synthesis. Science1980;207:315-317.
5.
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 Sci1983;32:2741-2745.
6.
6. Siler-Khodr TM, Khodr GS. Dose response analysis of GnRH stimulation of hCG release from human term placenta. Biol Reprod1981;25:353-358.
7.
7. Khodr GS, Siler-Khodr TM. The effect of luteinizing hormone releasing factor (LRF) on hCG secretion. Fertil Steril1979;30:301-304.
8.
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 somatommamotropin. Biol Reprod1986;34:245-254.
9.
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 Reprod1986;34:255-264.
10.
10. Siler-Khodr TM, Khodr GS, Valenzuela G, Harper MJ, Rhode J. GnRH effects on placental hormones during gestation. III. Prostaglandin E, prostaglandin F, and 13,14-dihydro-15-keto-prostaglandin F. Biol Reprod1986;35:312-319.
11.
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 Metab1990;70:1173-1178.
12.
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. Placenta1989;10:103-112.
13.
13. Siler-Khodr TM. Hypothalamic-like releasing hormones of the placenta. Clin Perinatol1983;10:553-566.
14.
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 USA1991;86:5114-5117.
15.
15. Cemerikic B, Maulik D, Ahmed MS. Opioids regulation of hCG release from trophoblast tissue is mediated by LHRH. Placenta1992;13:9A-9A (abstract).
16.
16. Petraglia F, Lim AT, Vale W. Adenosine 3′,5′-monophosphate, prostaglandins, and epinephrine stimulate the secretion of immunocreative gonadotropin-releasing hormone from cultured human placental cells. J Clin Endocrinol Metab1987;65:1020-1025.
17.
17. Barnea ER, Feldman D, Kaplan M. The effect of progesterone upon first trimester trophoblastic cell differentiation and human chrionic gonadotrophin secretion. Hum Reprod1991;6:905-909.
18.
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 Endoctrinol Metab1989;69:215-217.
19.
19. Radovick S, Wondisford FE, Nakayama Y, Yamada M, Cutler GB Jr, Weintraub BD. Isolation and characterization of the human gonadotropin-releasing hormone gene in the hypothalamus and placenta. Mol Endocrinol1990;4:476-480.
20.
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 USA1986;83:179-183.
21.
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. Endocrinology1993;133:2617-2623.
22.
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 Biol1991;10:411-421.
23.
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 Endocrinol1993;7:1654-1666.
24.
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 Endocrinol1996;117:241-246.
25.
25. Currie A, Fraser H, Sharpe R. Human placental receptors for luteinizing hormone releasing hormone. Biochem Biophys Res Commun1981;99:332-338.
26.
26. Iwashita M, Evans MI, Catt KJ. Characterization of a gonadotropin-releasing hormone receptor site in term lacenta and chorionic villi. J Clin Endocrinol Metab1986;62:127-133.
27.
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 Endocrinol1987;49:195-202.
28.
28. Bramley TA, McPhie CA. Menzies GS. Human placental gonadotrophin-releasing hormone (GnRH) binding sites: I. Characterization, properties and ligand specificity. Placenta1992;13:555-581.
29.
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 Metab1997;80:580-585.
30.
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. Endocrine1998;9:281-287.
31.
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 Reprod2000;4:999-1006.
32.
32. Cheng KW, Nathwani PS, Leung PCK. Regulation of human gonadotropin-releasing hormone receptor gene expression in placental cells. Endocrinology2000;141:2340-2349.
33.
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 Scand1994;73:284-289.
34.
34. Seshagiri PB, Terasaw 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 Reprod1994;9:1300-1307.
35.
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 Steril1984;41:448-454.
36.
36. Kang IS, Kuehl TJ, Siler-Khodr TM. Effect of treatment with gonadotropin-releasing hormone analogues on pregnancy outcome in the baboon. Fertil Steril1989;52:846-853.
37.
37. Gupta SK, Singh M. Characteristics and bioefficacy of monoclonal antigonadotropin releasing hormone antibody. Am J Reprod Immunol Microbiol1985;7:104-108.
38.
38. Das C, Gupta SK, Talwar GP. Pregnancy interfering action of LHRH and anti-LHRH. J Steroid Biochem1985;23:803-806.
39.
39. Hodges JK, Hearn JP. Effects of immunisation against luteinising hormone releasing hormone on reproduction of the marmoset monkey Callithrix jacchus. Nature1977;265:746-748.
40.
40. Das C, Talwar GP. Pregnancy-terminating action of a luteinizing hormone-releasing hormone agonist D-Ser(But)6desGly10ProEA in baboons. Fertil Steril1983;39:218-223.
41.
41. Rao A, Moudgal N. Effect of LHRH injection on serum chotrionic gonadotropin levels in the pregnant bonnet monkey (Macaca radiata). Obstet Gynecol1984;12:1105-1106.
42.
42. Rao AJ, Chakraborti R, Kotagi SG, Ravindranath N, Moudgal NR. Effect of LHRH agonists and antagonists in male and female bonnet monkeys (Macaca radiata). Steroid Biochem1985;23:807-809.
43.
43. Gautron JP, Pattou K, Kordon C. Occurrence of higher molecular forms of LHRH in fractionated extracts from rat hypothalamus, cortex and placenta. Mol Cell Endocrinol1981;24:1-15.
44.
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 Gynecol1991;165:1771-1776.
45.
45. King JA, Millar RP. Evolutionary aspects of gonadotropin-releasing hormone and its receptor. Cell Mol Neurobiol1995;15:5-23.
46.
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. Neuroendocrinology1993;58:166-177.
47.
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 Repr1994;54:467-477.
48.
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 Lett2000;435:199-203.
49.
49. White RB, Eisen JA, Kasten TL, Fernald RD. Second gene for gonadotropin-releasing hormone in humans. Med Sci2000;95:305-309.
50.
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 Endocrinol1999;162:117-126.
51.
51. Siler-Khodr TM, Grayson M. Action of chicken II GnRH on the human placenta. J Clin Endocrinol Metab2001;86:804-810.
52.
52. Hunter W, Greenwood FC. Preparation of iodine-131-labelled human growth hormone of high specific activity. Nature1962;194:495-496.
53.
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. Placenta1989;10:283-296.
54.
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;43,144-144 (Abstract 311).
55.
55. Kang IS, Siler-Khodr TM. Chorionic peptidase inactiviates GnRH as a post-proline peptidase. Placenta1992;13:81-87.
56.
56. Bramley TA, Menzies GS. Measurement of luteral and placental gonadotrophin-releasing hormone (GnRH) binding sites: Role of inactivation of GnRH tracer. Mol Hum Reprod1996;2:535-539.
57.
57. Siler-Khodr TM, Grayson M, Fashaw S. Inhibition of chorionic peptidase-1 (Case-1) activity by analogues of GnRH. J Soc Gynecol Invest1999;6,225A-225A (abstract).
