Skip to main content
SpringerLink
Log in

β-Core Fragment: Structure, Production, Metabolism, and Clinical Utility

  • Conference paper
Glycoprotein Hormones

Part of the book series: Serono Symposia USA ((SERONOSYMP))

  • 53 Accesses

Abstract

The β-core fragment of human chorionic gonadotropin (hCG) is a biologically inactive, small molecular weight molecule composed of the core portion of hCGβ-subunit. The fragment appears to be a major degradation production of hCG and hCGβ metabolism and is found in large amounts in the urine of pregnant women and some patients with malignancies. Smaller quantities are found in the blood and urine of nonpregnant normal individuals and patients with benign disorders. This chapter presents a historical perspective concerning the discovery of this molecule and discusses its purification, structure, origin, and clinical applications.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Matthies DL, Diczfalusy E. Differences in the physical properties of human chorionic gonadotrophin extracted from difference sources. Excerpta Medica (Amst) Int Congr ser no. 170, 1968: 34.

    Google Scholar 

  2. Matthies DL, Diczfalusy E. Relationship between physico-chemical, immunological and biological properties of human chorionic gonadotrophin, I. Properties of human chorionic gonadotrophin as found in tissues and body fluids. Acta Endocrinol (Copenh) 1971; 67: 434–44.

    CAS  Google Scholar 

  3. Franchimont P, Gaspard U, Reuter A, Heynen G. Polymorphism of protein and polypeptide hormones. Clin Endocrinol 1972; 1: 315–36.

    Article  CAS  Google Scholar 

  4. Vaitukaitis JL Immunologic and physical characterization of human chorionic gonadotropin (hCG) secreted by tumors. J Clin Endocrinol Metab 1973; 37: 505–14.

    Article  PubMed  CAS  Google Scholar 

  5. Vaitukaitis JL. Changing placental concentrations of human chorionic gonadotropin and its subunits during gestation. J Clin Endocrinol Metab 1974; 38: 755–60.

    Article  PubMed  CAS  Google Scholar 

  6. Vaitukaitis JL, Ebersole ER. Evidence for altered synthesis of human chorionic gonadotropin in gestational trophoblastic tumors. J Clin Endocrinol Metab 1976; 42: 1048–55.

    Article  PubMed  CAS  Google Scholar 

  7. Good A, Ramos-Uribe A, Ryan RJ, Kempers RD. Molecular forms of human chorionic gonadotropin in serum, urine, and placental extracts. Fertil Steril 1977; 28: 846–50.

    PubMed  CAS  Google Scholar 

  8. Hattori M, Yoshimoto Y, Matsukura S, Fujita T. Qualitative and quantitative analyses of human chorionic gonadotropin and its subunits produced by malignant tumors. Cancer 1980; 46: 355–61.

    Article  PubMed  CAS  Google Scholar 

  9. Papapetrou PD, Sakarelou NP, Braouzi H, Fessas Ph. Ectopic production of human chorionic gonadotropin (hCG) by neoplasms: the value of measurements of immunoreactive hCG in the urine as a screening procedure. Cancer 1980; 45: 2583–92.

    Article  PubMed  CAS  Google Scholar 

  10. Papapetrou PD, Nicopoulou S Ch. The origin of a human chorionic gonadotropin f3-subunit-core fragment excreted in the urine of patients with cancer. Acta Endocrinol 1986; 112: 415–22.

    PubMed  CAS  Google Scholar 

  11. Cole LA, Wang Y, Elliott M, et al. Urinary human chorionic gonadotropin free 0-subunit and 13-core fragment: a new marker of gynecologic cancer. Cancer Res 1988; 48: 1356–60.

    PubMed  CAS  Google Scholar 

  12. Cole LA, Schwartz PE, Wang Y. Urinary gonadotropin fragments (UGF) in cancers of the female reproductive system, I. Sensitivity and specificity, comparison with other markers. Gynecol Oncol 1988; 31: 82–90.

    Article  PubMed  CAS  Google Scholar 

  13. Wang Y, Schwartz PE, Chambers JT, Cole LA. Urinary gonadotropin fragments (UGF) in cancers of the female reproductive system, II. Initial serial studies. Gynecol Oncol 1988; 31: 91–100.

    Article  PubMed  CAS  Google Scholar 

  14. Cole LA, Nam J-H. Urinary gonadotropin fragment (UGF) measurements in the diagnosis and management of ovarian cancer. Yale J Biol Med 1989; 62: 367–78.

    PubMed  CAS  Google Scholar 

  15. Nam J-H, Cole LA, Chambers JT, Schwartz PE. Urinary gonadotropin fragment, a new tumor marker, I. Assay development and cancer specificity. Gynecol Oncol 1990; 36: 383–90.

    Article  PubMed  CAS  Google Scholar 

  16. Cole LA, Nam J-H, Chambers JT, Schwartz PE. Urinary gonadotropin fragment, a new tumor marker, II. Differentiating a benign from a malignant pelvic mass. Gynecol Oncol 1990; 36: 391–4.

    Article  PubMed  CAS  Google Scholar 

  17. Nam J-H, Chang K-C, Chambers JT, Schwartz PE, Cole LA. Urinary gonadotropin fragment, a new tumor marker, III. Use in cervical and vulvar cancers. Gynecol Oncol 1990; 38: 66–70.

    Article  PubMed  CAS  Google Scholar 

  18. Nam J-H, Chambers JT, Schwartz PE, Cole LA. Urinary gonadotropin fragment, a new tumor marker, IV. Use in endometrial cancer and uterine mixed mullerian tumors. Gynecol Oncol 1990; 39: 352–7.

    Article  PubMed  CAS  Google Scholar 

  19. Kardana A, Taylor ME, Southall PJ, Boxer GM, Rowan AJ, Bagshawe KD. Urinary gonadotrophin peptide-isolation and purification, and its immunohistochemical distribution in normal and neoplastic tissue. Br J Cancer 1988; 58: 281–6.

    Article  PubMed  CAS  Google Scholar 

  20. Iles RK, Jenkins BJ, Oliver RTD, Blandy JP, Chard T. Beta human chorionic gonadotrophin in serum and urine. A marker for metastatic urothelial cancer. Br J Urol 1989; 64: 241–4.

    Article  PubMed  CAS  Google Scholar 

  21. Lee CL, Iles RK, Shepherd JH, Hudson CN, Chard T. The purification and development of a radioimmunoassay for I3-core fragment of human chorionic gonadotrophin in urine: application as a marker of gynaecological cancer in premenopausal and postmenopausal women. J Endocrinol 1991; 130: 481–9.

    Article  PubMed  CAS  Google Scholar 

  22. Alfthan H, Haglund C, Roberts P, Stenman U-H. Elevation of free f3 subunit of human choriogonadotropin and core ß fragment of human choriogonadotropin in the serum and urine of patients with malignant pancreatic and biliary disease. Cancer Res 1992; 52: 4628–33.

    PubMed  CAS  Google Scholar 

  23. Kinugasa M, Nishimura R, Hasegawa K, et al. Assessment of urinary [3-core fragment of hCG as a tumor marker of cervical cancer. Acta Obstet Gynaecol Jpn 1992; 44: 188–94.

    CAS  Google Scholar 

  24. Wehmann RE, Nisula BC. Characterization of a discrete degradation production of the human chorionic gonadotropin [3-subunit in humans. J Clin Endocrinol Metab 1980; 51: 101–4.

    Article  PubMed  CAS  Google Scholar 

  25. Wehmann RE, Nisula BC. Metabolic and renal clearance rates of purified human chorionic gonadotropin. J Clin Invest 1981; 68: 184–94.

    Article  PubMed  CAS  Google Scholar 

  26. Wehmann RE, Amr S, Rosa C, Nisula BC. Metabolism, distribution and excretion of purified human chorionic gonadotropin and its subunits in man. Ann Endocrinol (Paris) 1984; 45: 291–5.

    CAS  Google Scholar 

  27. Lefort GP, Stolk JM, Nisula BC. Evidence that desialylation and uptake by hepatic receptors for galactose-terminated glycoproteins are immaterial to the metabolism of human choriogonadotropin in the rat. Endocrinology 1984; 115: 1551–7.

    Article  PubMed  CAS  Google Scholar 

  28. Lefort GP, Stolk JN, Nisula BC. Renal metabolism of the [3-subunit of human choriogonadotropin in the rat. Endocrinology 1986; 119: 924–31.

    Article  PubMed  CAS  Google Scholar 

  29. Blithe DL, Akar AH, Wehmann RE, Nisula BC. Purification of [3-core fragment from pregnancy urine and demonstration that its carbohydrate moieties differ from those of native human chorionic gonadotropin-f3. Endocrinology 1988; 122: 173–80.

    Article  PubMed  CAS  Google Scholar 

  30. Blithe DL, Wehmann RE, Nisula BC. Carbohydrate composition of β-core. Endocrinology 1989; 125: 2267–72.

    Article  PubMed  CAS  Google Scholar 

  31. Wehmann RE, Blithe DL, Flack MR, Nisula BC. Metabolic clearance rate and urinary clearance of purified β-core. J Clin Endocrinol Metab 1989; 69: 510–7.

    Article  PubMed  CAS  Google Scholar 

  32. Nisula BC, Blithe DL, Akar A, Lefort G, Wehmann RE. Metabolic fate of human choriogonadotropin. J Steroid Biochem 1989; 33: 733–7.

    Article  PubMed  CAS  Google Scholar 

  33. Wehmann RE, Blithe DL, Akar AH, Nisula BC. Disparity between β-core levels in pregnancy urine and serum: implications for the origin of urinary 13- core. J Clin Endocrinol Metab 1990; 70: 371–8.

    Article  PubMed  CAS  Google Scholar 

  34. Masure HR, Jaffee WL, Sickel MA, Birken S, Canfield RE, Vaitukaitis JL. Characterization of a small molecular size urinary immunoreactive human chorionic gonadotropin (hCG)-like substance produced by normal placenta and by hCG-secreting neoplasms. J Clin Endocrinol Metab 1981; 53: 1014–20.

    Article  PubMed  CAS  Google Scholar 

  35. Birken S, Armstrong EG, Kolks MAG, et al. Structure of the human chorionic gonadotropin β-core fragment from pregnancy urine. Endocrinology 1988; 123: 572–83.

    Article  PubMed  CAS  Google Scholar 

  36. Nishimura R, Endo Y, Tanabe K, Ashitaka Y, Tojo S. The biochemical properties of urinary human chorionic gonadotropin from the patients with trophoblastic diseases. J Endocrinol Invest 1981; 4: 349–58.

    PubMed  CAS  Google Scholar 

  37. Endo T, Nishimura R, Saito S, et al. Carbohydrate, structures of β-core fragment of human chorionic gonadotropin isolated from a pregnant individual. Endocrinology 1992; 130: 2052–8.

    Article  PubMed  CAS  Google Scholar 

  38. Akar AH, Wehmann RE, Blithe DL, Blacker C, Nisula BC. A radioimmunoassay for the core fragment of the human chorionic gonadotropin β- subunit. J Clin Endocrinol Metab 1988; 66: 538–45.

    Article  PubMed  CAS  Google Scholar 

  39. Krichevsky A, Armstrong EG, Schlatterer J, et al. Preparation and charac-terization of antibodies to the urinary fragment of the human chorionic gonadotropin 0-subunit. Endocrinology 1988; 123: 584–93.

    Article  PubMed  CAS  Google Scholar 

  40. O’Connor JF, Schlatterer JP, Birken S, et al. Development of highly sensitive immunoassays to measure human chorionic gonadotropin, its 13-subunit, and ß core fragment in the urine: application to malignancies. Cancer Res 1988; 48: 1361–6.

    PubMed  Google Scholar 

  41. Krichevsky A, Birken S, O’Connor J, et al. Development and characterization of a new, highly specific antibody to the human chorionic gonadotropin-13 fragment. Endocrinology 1991; 128: 1255–64.

    Article  PubMed  CAS  Google Scholar 

  42. Kardana A, Taylor ME, Rowan AJ, Read DA, Bagshawe KD. Characterisation of antibodies to urinary gonadotrophin peptide. J Immunol Methods 1989; 118: 53–8.

    Article  PubMed  CAS  Google Scholar 

  43. Alfthan H, Stenman U-H. Pregnancy serum contains the β-core fragment of human choriogonadotropin. J Clin Endocrinol Metab 1990; 70: 783–7.

    Article  PubMed  CAS  Google Scholar 

  44. deMedeiros SF, Amato F, Matthews CD, Norman RJ. Comparison of specific immunoassays for detection of the β-core human chorionic gonadotropin fragment in body fluids. J Endocrinol 1992; 135: 161–74.

    Article  CAS  Google Scholar 

  45. Kato Y, Kelley L, Braunstein GD. The beta-core fragment of human chorionic gonadotropin. In: Tomoda Y, Mizutani S, Narita O, Klopper A, eds. Placental and endometrial proteins: basic and clinical aspects. Utrecht, The Netherlands: VNU Science Press BV, 1988: 87–90.

    Google Scholar 

  46. Schroeder HR, Halter CM. Specificity of human 13-choriogonadotropin assays for the hormone and for an immunoreactive fragment present in urine during normal pregnancy. Clin Chem 1983; 29: 667–71.

    PubMed  CAS  Google Scholar 

  47. Kato Y, Braunstein GD. β-core fragment is a major form of immunoreactive urinary chorionic gonadotropin in human pregnancy. J Clin Endocrinol Metab 1988; 66: 1197–201.

    Article  PubMed  CAS  Google Scholar 

  48. Kardana A, Cole LA. Serum hCG 13-core fragment is masked by associated macromolecules. J Clin Endocrinol Metab 1990; 71: 1393–5.

    Article  PubMed  CAS  Google Scholar 

  49. Cole LA, Birken S. Origin and occurrence of human chorionic gonadotropin β-subunit core fragment. Mol Endocrinol 1988; 2: 825–30.

    Article  PubMed  CAS  Google Scholar 

  50. deMedeiros SF, Amato F, Matthews CD, Norman RJ. Urinary concentrations of beta core fragment of hCG throughout pregnancy. Obstet Gynecol 1992; 80: 223–8.

    CAS  Google Scholar 

  51. deMedeiros SF, Amato F, Bacich D, Wang L, Matthews CD, Norman RJ. Distributrion of the β-core human chorionic gonadotrophin fragment in human body fluids. J Endocrinol 1992; 135: 175–88.

    Article  CAS  Google Scholar 

  52. Amr S, Rosa C, Birken S, Canfield R, Nisula B. Carboxyterminal peptide fragments of the beta subunit are urinary products of the metabolism of desialylated human choriogonadotropin. J Clin Invest 1985; 76: 350–6.

    Article  PubMed  CAS  Google Scholar 

  53. Hussa RO. Biosynthesis of human chorionic gonadotropin. Endocr Rev 1980; 1: 268–94.

    Article  PubMed  CAS  Google Scholar 

  54. Bidart J-M, Puisieux A, Troalen F, Foglietti M-J, Bohuon C, Bellet D. Characterization of a cleavage product in the human choriogonadotropin 13- subunit. Biochem Biophys Res Commun 1988; 154: 626–32.

    Article  PubMed  CAS  Google Scholar 

  55. Puisieux A, Bellet D, Troalen F, et al. Occurrence of fragmentation of free and combined forms of the 0-subunit of human chorionic gonadotropin. Endocrinology 1990; 126: 687–94.

    Article  PubMed  CAS  Google Scholar 

  56. Lustbader JW, Birken S, Pileggi NF, et al. Crystallization and characterization of human chorionic gonadotropin in chemically deglycosylated and enzymatically desialylated states. Biochemistry 1989; 28: 9239–43.

    Article  PubMed  CAS  Google Scholar 

  57. Sakakibara R, Miyazaki S, Ishiguro M. A nicked 13-subunit of human chorionic gonadotropin purified from pregnancy urine. J Biochem 1990; 107: 858–62.

    PubMed  CAS  Google Scholar 

  58. Cole LA, Kardana A, Ying FC, Birken S. The biological and clinical significance of nicks in human chorionic gonadotropin and its free β-subunit. Yale J Biol Med 1991; 64: 627–37.

    PubMed  CAS  Google Scholar 

  59. Kardana A, Elliott MM, Gawinowicz M-A, Birken S, Cole LA. The heterogeneity of human chorionic gonadotropin (hCG), I. Characterization of peptide heterogeneity in 13 individual preparations of hCG. Endocrinology 1991; 129: 1541–50.

    Article  PubMed  CAS  Google Scholar 

  60. Birken S, Gawinowicz MA, Kardana A, Cole LA. The heterogeneity of human chorionic gonadotropin (hCG), II. Characteristics and origins of nicks in hCG reference standards. Endocrinology 1991; 129: 1551–8.

    Article  PubMed  CAS  Google Scholar 

  61. Cole LA, Kardana A, Andrade-Gordon P, et al. The heterogeneity of human chorionic gonadotropin (hCG), III. The occurrence and biological and immunological activities of nicked hCG. Endocrinology 1991; 129: 1559–67.

    Article  PubMed  CAS  Google Scholar 

  62. Cole LA, Kardana A, Park S-Y, Braunstein GD. The deactivation of hCG by nicking and dissociation. J Clin Endocrinol Metab 1993: 76.

    Google Scholar 

  63. Markkanen SO, Rajaniemi HJ. Uptake and subcellular catabolism of human choriogonadotropin in proximal tubule cells of rat kidney. Mol Cell Endocrinol 1979; 13: 181–90.

    Article  PubMed  CAS  Google Scholar 

  64. Alfthan H, Haglund C, Dabek J, Stenman U-H. Concentrations of human choriogonadotropin, its 0-subunit, and the core fragment of the 13-subunit in serum and urine of men and nonpregnant women. Clin Chem 1992; 38: 1981–7.

    PubMed  CAS  Google Scholar 

  65. Akar AH, Gervasi G, Blacker C, Wehmann RE, Blithe DL, Nisula BC. Human chorionic gonadotropin-like and β-core-like materials in postmenopausal urine. J Endocrinol 1990; 125: 477–84.

    Article  PubMed  CAS  Google Scholar 

  66. Iles RK, Lee CL, Howes I, Davies S, Edwards R, Chard T Immunoreactive β-core-like material in normal postmenopausal urine: human chorionic gonadotrophin or LH origin? Evidence for the existence of LH core. J Endocrinol 1992; 133: 459–66.

    Article  PubMed  CAS  Google Scholar 

  67. Braunstein GD. Production of human chorionic gonadotropin by nontrophoblastic tumors and tissues. In: Tomoda Y, Mizutani S, Narita O, Klopper A, eds. Placental and endometrial proteins: basic and clinical aspects. Utrecht, The Netherlands: VNU Science Press BV, 1988: 493–502.

    Google Scholar 

  68. Odell WD, Griffin J, Sawitzke A. Chorionic gonadotropin secretion in normal, nonpregnant humans. Trends Endocrinol Metab 1990; 1: 418–21.

    Article  PubMed  CAS  Google Scholar 

  69. Norman RJ, Buck RH, Aktar B, Mayet N, Moodley J. Detection of a small molecular species of human chorionic gonadotropin in the urine of patients with carcinoma of the cervix and cervical intraepithelial neoplasia: comparison with other assays for human chorionic gonadotropin and its fragments. Gynecol Oncol 1990; 37: 254–9.

    Article  PubMed  CAS  Google Scholar 

  70. deMedeiros SF, Amato F, Norman RJ. Stability of immunoreactive β-core fragment of hCG. Obstet Gynecol 1991; 77: 53–9.

    CAS  Google Scholar 

  71. Wehmarin RE, Blithe DL, Akar AH, Nisula BC. β-core fragments are contaminants of the World Health Organization Reference Preparations of human choriogonadotrophin and its a-subunit. J Endocrinol 1988; 117: 147–52.

    Article  Google Scholar 

  72. Maruo T, Kitajima T, Otani T, et al. Clinical significance of the measurement of urinary hCG-13-core fragment in patients with gynecologic malignant tumors. Obstet Gynecol Jpn 1991; 7: 1197–202.

    Google Scholar 

  73. Tanaka J, Takashi M, Okamura K, Shimochi T, Miyake K, Yamasaki H. Significance of hCGO-core fragment in kidney lesions and urinary tract and bladder cancer [Abstract]. 12th Tumor Marker Assoc meet, Osaka, Japan, 1992.

    Google Scholar 

  74. Negishi N, Iwabuchi H, Sakunaga H, Okabe K. Clinical significance of UGP in gynecological tumors [Abstract]. 12th Tumor Marker Assoc meet, Osaka, Japan, 1992.

    Google Scholar 

  75. Braunstein GD. Placental proteins as tumor markers. In: Herberman RB, Mercer DW, eds. Immunodiagnosis of cancer. New York: Marcel Dekker, 1990: 673–701.

    Google Scholar 

  76. Yamanaka N, Morisue K, Kawabata G, Hama M, Nishimura R. Significance of hCG β-core fragment as a tumor marker in bladder cancer [Abstract]. 12th Tumor Marker Assoc meet, Osaka, Japan, 1992.

    Google Scholar 

  77. McGill J, Cole L, Nam JH, et al. Urinary gonadotropin fragment (UGF): a potential marker of colorectal cancer. J Tumor Marker Oncol 1990; 5: 175–7.

    Google Scholar 

  78. D’Agostino RS, Cole LA, Ponn RB, Stern H, Schwartz PE. Urinary gonadotropin fragment measurement in patients with lung and esophageal disease. J Surg Oncol 1992; 49: 147–50.

    Article  PubMed  Google Scholar 

Download references

Authors
  1. Glenn D. Braunstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Irving Center for Clinical Research Columbia University College of Physicians and Surgeons, 10032, New York, NY, USA

    Joyce W. Lustbader Ph.D.

  2. Department of Biochemistry, University of Georgia, 30602, Athens, GA, USA

    David Puett Ph.D.

  3. Eppley Institute for Research, University of Nebraska Medical Center, 68198, Omaha, NE, USA

    Raymond W. Ruddon M.D., Ph.D.

Rights and permissions

Reprints and permissions

Copyright information

© 1994 Springer-Verlag New York, Inc.

About this paper

Cite this paper

Braunstein, G.D. (1994). β-Core Fragment: Structure, Production, Metabolism, and Clinical Utility. In: Lustbader, J.W., Puett, D., Ruddon, R.W. (eds) Glycoprotein Hormones. Serono Symposia USA. Springer, New York, NY. https://doi.org/10.1007/978-1-4613-8386-4_22

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-8386-4_22

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4613-8388-8

  • Online ISBN: 978-1-4613-8386-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation