Horm Metab Res 2004; 36(2): 75-77
DOI: 10.1055/s-2004-814209
Hypothesis
© Georg Thieme Verlag Stuttgart · New York

hCG Urinary Metabolites in Breast Milk

J.  M.  Sutton1 , S.  A.  Khanlian1 , L.  A.  Cole1 , S.  A.  Butler2, 3
  • 1Division of Women’s Health Research, Dept. Obstetrics and Gynecology, University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
  • 2Williamson Laboratory, Dept. of Obstetrics and Gynaecology, St. Bartholomew’s Hospital, London, UK
  • 3Diagnostica Medica, Centro Fisopatologia della Reproduzione, Mercogliano, Avellino, Italy
Further Information

Publication History

Received 8 July 2003

Accepted without revision 18 August 2003

Publication Date:
05 March 2004 (online)

Introduction

Human chorionic gonadotropin (hCG) is the glycoprotein hormone associated with the onset of pregnancy. The molecule can be detected in maternal serum and urine following implantation [1], and assays for hCG have been used to detect and monitor pregnancy for over 70 years [2] [3]. During pregnancy, hCG has also been detected in saliva [4] [5]. hCG is a heterodimer consisting of two subunits, α and β, held together non-covalently. Dissociation of the α and β subunits initiates the metabolism of hCG and results in the terminal hCG breakdown product β-core fragment (hCGβcf), which is found in renal tissue only [6] [7] [8] and is present at high concentrations in urine samples [8] [9] [10] [11] [12] [13] [14] [15]. Since hCGβcf is hardly detectable in serum, it is generally assumed that the kidney is the major breakdown site of hCG metabolism.

Breast-feeding can provide protection against pregnancy for up to six months postpartum [16]. During breastfeeding, prolactin mediates the cessation of menses by suppressing pituitary LH and FSH [17], and it is therefore quite uncommon for a breast-feeding mother to become pregnant. This is the likely reason why there have been no previous investigations on hCG in breast milk in pregnant breastfeeding mothers. To examine the metabolism of hCG, we investigated the concentrations of intact hCG (hCG), hCG free beta subunit (hCGβ), nicked hCG cleaved at p47 - 48 (N-hCG), hCGβcf, and hyperglycosylated hCG (H-hCG) in the serum, urine, saliva, and breast milk of a lactating pregnant woman.

References

  • 1 Braunstein G D, Rasor J, Adler D, Danzer H, Wade M E. Serum human chorionic gonadotrophin levels throughout pregnancy.  Am J Obs Gyn. 1976;  126 678-681
  • 2 Aschheim S, Zondek B. Das Hormon des Hypophysenvorderlappens: Testobjekt zum Nachweis des Hormons.  Klin Wochenschr. 1927;  6 248-252
  • 3 Wide L, Gemzell C A. An immunological pregnancy test.  Acta Endocrinol. 1960;  35 261-267
  • 4 Turkes A, Pennington G W, Griffiths K. Determination of human chorionic gonadotrophin (beta subunit) in saliva and its role in trophoblastic diseases.  Br J Cancer Clin Oncol. 1984;  20 291-292
  • 5 Vining R F, McGinley R A, Symons R G. Hormones in saliva: mode of entry and consequent implications for interpretation.  Clin Chem. 1983;  29 1752-1756
  • 6 Markkanen S O, Tollikko K, Vanha-Perttula T, Rajaniemi H. Disappearance of human 125I chorionic gonadotrophin from the circulation of the rat: tissue uptake and degradation.  Endocrinology. 1979;  104 1540-1547
  • 7 Wehmann R E, Nisula B C. The metabolic and renal clearance rates of purified hCG.  J Clin Endocrinol. 1981;  68 184-194
  • 8 Lefort G P, Stolk J M, Nisula B C. Renal metabolism of the beta-subunit of human choriogonadotropin in the rat.  Endocrinology. 1986;  119 924-931
  • 9 Cole L A, Seifer D B, Kardana A, Braunstein G D. Selecting human chorionic gonadotropin immunoassays: Consideration of crossreacting molecules in first trimester pregnancy serum and urine.  Am J Obstet Gynecol.. 1993;  168 580-1586
  • 10 Birken S, Armstrong E G, Kolks M AG, Cole L A, Agosto G M, Krichevsky A. et al . Structure of human chorionic gonadotropin β-subunit core fragment from pregnancy urine.  Endocrinology. 1988;  123 572-580
  • 11 Bidart J-M, Puisieux A, Troalen F, Foglietti M J, Bohuon C, Bellet D. Characterization of the cleavage product in the human choriogonadotropin β-subunit.  Biochem Biophys Res Comm.. 1988;  154 626-632
  • 12 Alfthan H, Stenman U H. Pregnancy serum contains the beta-core fragment of human choriogonadotropin.  J Clin Endocrinol Metab. 1990;  70 783-787
  • 13 Kardana A, Cole L A. Human chorionic gonadotropin β-subunit nicking enzymes in pregnancy and cancer patient serum.  J Clin Endocrinol Metab.. 1994;  79 761-767
  • 14 Cole L A. Immunoassay of hCG, its Free Subunits and Metabolites.  Clin Chem.. 1997;  43 2233-2243
  • 15 Wehmann R E, Blithe D L, Akar A H, Nisula B C. Disparity between beta-core levels in pregnancy urine and serum: implications for the origin of urinary beta-core.  J Clin Endocrinol Metab.. 1990;  70 371-378
  • 16 Kennedy K I, van Look P FA, von Hertzen H, Ayeni 0, Pinol A PY. World Health Organization multinational study of breast-feeding and lactational amenorrhea.  Fertil Steril.. 1999;  72 431-447
  • 17 McNeilly A S. Lactaional amenorrhea.  Endocrinol Metab Clin North Am.. 1993;  22 59-73
  • 18 Cole L A, Shahabi S, Oz U A, Bahado-Singh R O, Mahoney M J. Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: A new basis for gestational down syndrome Screening.  Clin Chem.. 1999;  45 2109-2119
  • 19 Bertino E, Prandi G M, Fabris C. et al . Human milk proteins may interfere in ELISA measurements of bovine β-lactoglobulin in human milk.  Acta Paediatr. 1996;  85 543-549
  • 20 Wehmann R E, Blithe D L, Flack M R, Nisula B C. Metabolic clearance rate and urinary clearance of purified beta-core.  J Clin Endocrinol Metab. 1989;  69 510-517
  • 21 Cole L A, Birken S. Origin and occurrence of human chorionic gonadotropin beta-subunit core fragment.  Mol Endocrinol. 1988;  2 825-830
  • 22 Birken S, Maydelman Y, Gawinowicz M A, Pound A, Liu Y, Hartee A S. Isolation and characterization of human pituitary chorionic gonadotropin.  Endocrinology. 1996;  137 1402-1411
  • 23 Hoermann R, Spoettl G, Berger P, Mann K. Immunoreactive human chorionic gonadotrophin p core fragment in human pituitary.  Exp Clin Endo Diab.. 1995;  103 24-331
  • 24 Kinabo L D, Nielsen P. Renal handling and mammary excretion of sulfatroxazole in goats.  Research Communications in Chem Path Pharm. 1988;  60 265-268

Dr. S. A. Butler

Williamson Laboratory

Bartholomew’s Hospital · West Smithfield · London · EC1A 7BE · UK

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