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hCG and Its Disruption by Environmental Contaminants during Human Pregnancy
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Human Chorionic Gonadotropin (hCG)—An Endocrine, Regulator of Gestation and Cancer

Department of Obsterics and Gynecology, University Hospital, LMU Munich, 81377 Munich, Germany
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(5), 1502;
Original submission received: 19 April 2018 / Revised: 15 May 2018 / Accepted: 17 May 2018 / Published: 17 May 2018
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
Human Chorionic Gonadotropin (hCG) is a heterodimeric glycoprotein composed of two subunits [1]. This important and very complex molecule, that exists in different molecular forms, is implicated in all major reproductive and developmental processes in humans [1,2]. Although the title implies that hCG is an endocrine regulator, we are aware that hCG actions during pregnancy (except luteal regulation) and in cancers are largely paracrine and/or autocrine in nature. In the last years, the significance and the importance of hCG have really expanded, and many studies suggest an important role of this glycoprotein in the field of pregnancy.
hCG is secreted by the syncytiotrophoblast which originates from fused and differentiated cytotrophoblast cells [3,4]. For a long time, the main known role of hCG was the promotion of progesterone secretion by the corpus luteum in early pregnancy, acting via the hCG/LH (luteinizing hormone) receptor. However, more recently, many other functions of hCG, not only in the placenta but also in the myometrium, the uterus, and the fetus, have been described [5,6,7].
In addition, the LH/hCG receptor is also expressed on granulosa cells. Casarini et al. have reported that the signaling pathways of hCG and LH do not completely overlap, and this fact may have implications for hCG use in assisted reproductive techniques (ART) [8]. Hershko Klement et al. described that a gonadotropin-releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering a GnRH agonist followed by hCG triggering [9].
hCG promotes angiogenesis and vascular genesis in the uterine vasculature during pregnancy [10,11], whereas its role in placental growth and development is incontrovertible. The hCG/LH receptor was also found in fetal organs, and thus it is suggested that hCG plays an important role in organ growth and differentiation in the fetus [12,13,14]. A function for hCG in umbilical cord growth and development has also been reported in the literature [15]. Many additional different immunomodulatory effects of hCG are described [16,17,18].
Schumacher et al. found that hCG determines fetal fate by regulating maternal innate and adaptive immune responses, allowing the acceptance of the foreign fetal antigens [19]. Environmental pollution can disturb hCG function during pregnancy. Paulescu et al. showed that prenatal exposure to selected endocrine-disrupting chemicals like Bisphenol A can have a deleterious impact on the fetus and long-lasting consequences also in adult life [2].
Some new data have shown a function of hCG in the implantation process [20,21]. Makrigiannakis et al. showed that hCG is one of the key molecules during the process of implantation. hCG effectively modulates several metabolic pathways within the decidua, contributing to endometrial receptivity [22]. In addition, the hCG/LH receptor has also been identified in adults women’s brain, a finding that could explain the hyperemesis gravidarum during pregnancy [23].
The expression of hCG is observed in several types of malignancies, including prostate cancer [24], colorectal cancer [25], lung adenocarcinoma [26], and different gynecological cancers, such as endometrial adenocarcinoma, breast cancer [27], cervical carcinoma [28], and ovarian cancer [29], and is associated with especially poorly differentiated and high-grade tumors [30]. Human chorionic gonadotrophin may be also a possible mediator of leiomyoma growth during pregnancy [31].
Finally, Theofanakis et al. showed that hCG could have a potential role as an anti-rejection agent in solid organ transplantation [32].
In summary, hCG is a multifaceted hormone with a very wide range of actions. In this Special Issue, “hCG—An Endocrine, Regulator of Gestation and Cancer” we have tried to highlight the different functional aspects of hCG and give a promising insight into different pathophysiological aspects, clinical applications, and therapeutic options related to hCG.

Conflicts of Interest

The authors declare no conflict of interest.


  1. Lund, H.; Paus, E.; Berger, P.; Stenman, U.H.; Torcellini, T.; Halvorsen, T.G.; Reubsaet, L. Epitope analysis and detection of human chorionic gonadotropin (hCG) variants by monoclonal antibodies and mass spectrometry. Tumour Biol. 2014, 35, 1013–1022. [Google Scholar] [CrossRef] [PubMed]
  2. Paulesu, L.; Rao, C.V.; Ietta, F.; Pietropolli, A.; Ticconi, C. hCG and its disruption by environmental contaminants during human pregnancy. Int. J. Mol. Sci. 2018, 19, 914. [Google Scholar] [CrossRef] [PubMed]
  3. Choi, J.; Smitz, J. Luteinizing hormone and human chorionic gonadotropin: Origins of difference. Mol. Cell. Endocrinol. 2014, 383, 203–213. [Google Scholar] [CrossRef] [PubMed]
  4. Nwabuobi, C.; Arlier, S.; Schatz, F.; Guzeloglu-Kayisli, O.; Lockwood, C.J.; Kayisli, U.A. hCG: Biological functions and clinical applications. Int. J. Mol. Sci. 2017, 18, 2037. [Google Scholar] [CrossRef] [PubMed]
  5. Cole, L.A. Biological functions of hCG and hCG-related molecules. Reprod. Biol. Endocrinol. 2010, 8, 102. [Google Scholar] [CrossRef] [PubMed]
  6. Guibourdenche, J.; Fournier, T.; Malassine, A.; Evain-Brion, D. Development and hormonal functions of the human placenta. Folia Histochem. Cytobiol. 2009, 47, S35–S40. [Google Scholar] [CrossRef] [PubMed]
  7. Cole, L.A. Hyperglycosylated hCG, a review. Placenta 2010, 31, 653–664. [Google Scholar] [CrossRef] [PubMed]
  8. Casarini, L.; Riccetti, L.; De Pascali, F.; Gilioli, L.; Marino, M.; Vecchi, E.; Morini, D.; Nicoli, A.; La Sala, G.B.; Simoni, M. Estrogen modulates specific life and death signals induced by LH and hCG in human primary granulosa cells in vitro. Int. J. Mol. Sci. 2017, 18, 926. [Google Scholar] [CrossRef] [PubMed]
  9. Hershko Klement, A.; Shulman, A. hCG triggering in art: An evolutionary concept. Int. J. Mol. Sci. 2017, 18, 1075. [Google Scholar] [CrossRef] [PubMed]
  10. Berndt, S.; Blacher, S.; Perrier d’Hauterive, S.; Thiry, M.; Tsampalas, M.; Cruz, A.; Pequeux, C.; Lorquet, S.; Munaut, C.; Noel, A.; et al. Chorionic gonadotropin stimulation of angiogenesis and pericyte recruitment. J. Clin. Endocrinol. Metab. 2009, 94, 4567–4574. [Google Scholar] [CrossRef] [PubMed]
  11. Zygmunt, M.; Herr, F.; Keller-Schoenwetter, S.; Kunzi-Rapp, K.; Munstedt, K.; Rao, C.V.; Lang, U.; Preissner, K.T. Characterization of human chorionic gonadotropin as a novel angiogenic factor. J. Clin. Endocrinol. Metab. 2002, 87, 5290–5296. [Google Scholar] [CrossRef] [PubMed]
  12. De Medeiros, S.F.; Norman, R.J. Human choriogonadotrophin protein core and sugar branches heterogeneity: Basic and clinical insights. Hum. Reprod. Update 2009, 15, 69–95. [Google Scholar] [CrossRef] [PubMed]
  13. Nisikori, K.; Nagoshi, K.; Shimizu, K.; Yoshida, N. Assessment of fetal growth and serum hCG titers after in vitro fertilization and embryo transfer. Int. J. Gynaecol. Obstet. 1993, 41, 147–152. [Google Scholar] [CrossRef]
  14. Rotsztejn, D.; Rana, N.; Dmowski, W.P. Correlation between fetal heart rate, crown-rump length, and beta-human chorionic gonadotropin levels during the first trimester of well-timed conceptions resulting from infertility treatment. Fertil. Steril. 1993, 59, 1169–1173. [Google Scholar] [CrossRef]
  15. Rao, C.V.; Li, X.; Toth, P.; Lei, Z.M.; Cook, V.D. Novel expression of functional human chorionic gonadotropin/luteinizing hormone receptor gene in human umbilical cords. J. Clin. Endocrinol. Metab. 1993, 77, 1706–1714. [Google Scholar] [PubMed]
  16. Akoum, A.; Metz, C.N.; Morin, M. Marked increase in macrophage migration inhibitory factor synthesis and secretion in human endometrial cells in response to human chorionic gonadotropin hormone. J. Clin. Endocrinol. Metab. 2005, 90, 2904–2910. [Google Scholar] [CrossRef] [PubMed]
  17. Schumacher, A.; Heinze, K.; Witte, J.; Poloski, E.; Linzke, N.; Woidacki, K.; Zenclussen, A.C. Human chorionic gonadotropin as a central regulator of pregnancy immune tolerance. J. Immunol. 2013, 190, 2650–2658. [Google Scholar] [CrossRef] [PubMed]
  18. Lei, Z.M.; Yang, M.; Li, X.; Takikawa, O.; Rao, C.V. Upregulation of placental indoleamine 2,3-dioxygenase by human chorionic gonadotropin. Biol. Reprod. 2007, 76, 639–644. [Google Scholar] [CrossRef] [PubMed]
  19. Schumacher, A. Human chorionic gonadotropin as a pivotal endocrine immune regulator initiating and preserving fetal tolerance. Int. J. Mol. Sci. 2017, 18, 2166. [Google Scholar] [CrossRef] [PubMed]
  20. Licht, P.; Fluhr, H.; Neuwinger, J.; Wallwiener, D.; Wildt, L. Is human chorionic gonadotropin directly involved in the regulation of human implantation? Mol. Cell. Endocrinol. 2007, 269, 85–92. [Google Scholar] [CrossRef] [PubMed]
  21. Perrier d’Hauterive, S.; Berndt, S.; Tsampalas, M.; Charlet-Renard, C.; Dubois, M.; Bourgain, C.; Hazout, A.; Foidart, J.M.; Geenen, V. Dialogue between blastocyst hCG and endometrial LH/hCG receptor: Which role in implantation? Gynecol. Obstet. Investig. 2007, 64, 156–160. [Google Scholar] [CrossRef] [PubMed]
  22. Makrigiannakis, A.; Vrekoussis, T.; Zoumakis, E.; Kalantaridou, S.N.; Jeschke, U. The role of hCG in implantation: A mini-review of molecular and clinical evidence. Int. J. Mol. Sci. 2017, 18, 1305. [Google Scholar] [CrossRef] [PubMed]
  23. Lei, Z.M.; Rao, C.V.; Kornyei, J.L.; Licht, P.; Hiatt, E.S. Novel expression of human chorionic gonadotropin/luteinizing hormone receptor gene in brain. Endocrinology 1993, 132, 2262–2270. [Google Scholar] [CrossRef] [PubMed]
  24. Sheaff, M.T.; Martin, J.E.; Badenoch, D.F.; Baithun, S.I. Beta hCG as a prognostic marker in adenocarcinoma of the prostate. J. Clin. Pathol. 1996, 49, 329–332. [Google Scholar] [CrossRef] [PubMed]
  25. Lundin, M.; Nordling, S.; Carpelan-Holmstrom, M.; Louhimo, J.; Alfthan, H.; Stenman, U.H.; Haglund, C. A comparison of serum and tissue hCG beta as prognostic markers in colorectal cancer. Anticancer Res. 2000, 20, 4949–4951. [Google Scholar] [PubMed]
  26. Wong, Y.P.; Tan, G.C.; Aziz, S.; Pongprakyun, S.; Ismail, F. Beta-human chorionic gonadotropin-secreting lung adenocarcinoma. Malays. J. Med. Sci. 2015, 22, 76–80. [Google Scholar] [PubMed]
  27. Kolbl, A.C.; Schlenk, K.; Behrendt, N.; Andergassen, U. The importance of hCG in human endometrial adenocarcinoma and breast cancer. Int. J. Biol. Markers 2018, 33, 33–39. [Google Scholar] [CrossRef] [PubMed]
  28. Crawford, R.A.; Iles, R.K.; Carter, P.G.; Caldwell, C.J.; Shepherd, J.H.; Chard, T. The prognostic significance of beta human chorionic gonadotrophin and its metabolites in women with cervical carcinoma. J. Clin. Pathol. 1998, 51, 685–688. [Google Scholar] [CrossRef] [PubMed]
  29. Lenhard, M.; Tsvilina, A.; Schumacher, L.; Kupka, M.; Ditsch, N.; Mayr, D.; Friese, K.; Jeschke, U. Human chorionic gonadotropin and its relation to grade, stage and patient survival in ovarian cancer. BMC Cancer 2012, 12, 2. [Google Scholar] [CrossRef] [PubMed]
  30. Schuler-Toprak, S.; Treeck, O.; Ortmann, O. Human chorionic gonadotropin and breast cancer. Int. J. Mol. Sci. 2017, 18, 1587. [Google Scholar] [CrossRef] [PubMed]
  31. Sarais, V.; Cermisoni, G.C.; Schimberni, M.; Alteri, A.; Papaleo, E.; Somigliana, E.; Vigano, P. Human chorionic gonadotrophin as a possible mediator of leiomyoma growth during pregnancy: Molecular mechanisms. Int. J. Mol. Sci. 2017, 18, 2014. [Google Scholar] [CrossRef] [PubMed]
  32. Theofanakis, C.; Drakakis, P.; Besharat, A.; Loutradis, D. Human chorionic gonadotropin: The pregnancy hormone and more. Int. J. Mol. Sci. 2017, 18, 1059. [Google Scholar] [CrossRef]

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Heidegger, H.; Jeschke, U. Human Chorionic Gonadotropin (hCG)—An Endocrine, Regulator of Gestation and Cancer. Int. J. Mol. Sci. 2018, 19, 1502.

AMA Style

Heidegger H, Jeschke U. Human Chorionic Gonadotropin (hCG)—An Endocrine, Regulator of Gestation and Cancer. International Journal of Molecular Sciences. 2018; 19(5):1502.

Chicago/Turabian Style

Heidegger, Helene, and Udo Jeschke. 2018. "Human Chorionic Gonadotropin (hCG)—An Endocrine, Regulator of Gestation and Cancer" International Journal of Molecular Sciences 19, no. 5: 1502.

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