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Special Issue "hCG—An Endocrine, Regulator of Gestation and Cancer"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2017)

Special Issue Editor

Guest Editor
Prof. Dr. Udo Jeschke

Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians Universität München, 80337 Munich, Germany
Website | E-Mail
Interests: hCG; placenta; reproductive immunology; gynecologic oncology; glycoproteins

Special Issue Information

Dear Colleagues,

Human chorionic gonadotropin is a pregnancy hormone and, in addition, a complex glycoprotein with a molecular mass of about 37 kDa. It is composed of two glycosylated subunits, which are associated non-covalently. It is produced in the placental syncytiotrophoblast and in a large number of different tumours. Like the pituitary gonadotropins LH (luteinizing hormone), FSH (follicle-stimulating hormone) and TSH (thyroid-stimulating hormone), it is a heterodimer and composed of an alpha-subunit, which is common for the glycoprotein family and a specific β-subunit. There are five major isoforms of hCG: 1: hCG, 2: sulfated hCG, 3: hyperglycosylated hCG, 4: hCG free β-subunit and 5: hyperglycosylated hCG free β-subunit. The most often described function of hCG is its role in pregnancy. Human chorionic gonadotropin is the essential hormone to maintain pregnancy. It controls the implantation and the development of the placenta. It also controls the transformation of the corpus luteum to gravid corpus, which, in turn, obtains the production of progesterone and estradiol in the first weeks of pregnancy. On the other hand, there are several types of malignancies including bladder carcinoma, lung cancer, colorectal carcinoma, prostate cancer, gastric carcinomas and different gynecological cancers like breast cancer, cervical carcinoma, vulva/vaginal cancer which express hCG or its subunits ectopically. Therefore this special issue will deal on this entire different expression pattern and will also deal with functional aspects of hCG.

Prof. Dr. Udo Jeschke
Guest Editor

Manuscript Submission Information

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Keywords

  • hCG
  • trophoblast
  • disturbed pregnancy
  • oncology
  • G-Protein coupled receptor pathways

Published Papers (10 papers)

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Editorial

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Open AccessEditorial Human Chorionic Gonadotropin (hCG)—An Endocrine, Regulator of Gestation and Cancer
Int. J. Mol. Sci. 2018, 19(5), 1502; https://doi.org/10.3390/ijms19051502
Received: 19 April 2018 / Revised: 15 May 2018 / Accepted: 17 May 2018 / Published: 17 May 2018
Cited by 1 | PDF Full-text (165 KB) | HTML Full-text | XML Full-text
Abstract
Human Chorionic Gonadotropin (hCG) is a heterodimeric glycoprotein composed of two subunits [...] Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)

Research

Jump to: Editorial, Review

Open AccessArticle 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(5), 926; https://doi.org/10.3390/ijms18050926
Received: 28 February 2017 / Revised: 31 March 2017 / Accepted: 25 April 2017 / Published: 28 April 2017
Cited by 11 | PDF Full-text (2122 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro- and anti-apoptotic effect of 100 pM LH or hCG, in the presence or
[...] Read more.
Luteinizing hormone (LH) and human chorionic gonadotropin (hCG) are glycoprotein hormones used for assisted reproduction acting on the same receptor (LHCGR) and mediating different intracellular signaling. We evaluated the pro- and anti-apoptotic effect of 100 pM LH or hCG, in the presence or in the absence of 200 pg/mL 17β-estradiol, in long-term, serum-starved human primary granulosa cells (hGLC) and a transfected granulosa cell line overexpressing LHCGR (hGL5/LHCGR). To this purpose, phospho-extracellular-regulated kinase 1/2 (pERK1/2), protein kinase B (pAKT), cAMP-responsive element binding protein (pCREB) activation and procaspase 3 cleavage were evaluated over three days by Western blotting, along with the expression of target genes by real-time PCR and cell viability by colorimetric assay. We found that LH induced predominant pERK1/2 and pAKT activation STARD1, CCND2 and anti-apoptotic XIAP gene expression, while hCG mediated more potent CREB phosphorylation, expression of CYP19A1 and procaspase 3 cleavage than LH. Cell treatment by LH is accompanied by increased (serum-starved) cell viability, while hCG decreased the number of viable cells. The hCG-specific, pro-apoptotic effect was blocked by a physiological dose of 17β-estradiol, resulting in pAKT activation, lack of procaspase 3 cleavage and increased cell viability. These results confirm that relatively high levels of steroidogenic pathway activation are linked to pro-apoptotic signals in vitro, which may be counteracted by other factors, i.e., estrogens. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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Review

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Open AccessReview hCG and Its Disruption by Environmental Contaminants during Human Pregnancy
Int. J. Mol. Sci. 2018, 19(3), 914; https://doi.org/10.3390/ijms19030914
Received: 8 March 2018 / Revised: 16 March 2018 / Accepted: 17 March 2018 / Published: 20 March 2018
Cited by 2 | PDF Full-text (625 KB) | HTML Full-text | XML Full-text
Abstract
Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues.
[...] Read more.
Human chorionic gonadotropin (hCG) is a hormone of considerable importance in the establishment, promotion and maintenance of human pregnancy. It has been clearly demonstrated that hCG exerts multiple endocrine, paracrine and autocrine actions on a variety of gestational and non-gestational cells and tissues. These actions are directed to promote trophoblast invasiveness and differentiation, placental growth, angiogenesis in uterine vasculature, hormone production, modulation of the immune system at the maternal-fetal interface, inhibition of myometrial contractility as well as fetal growth and differentiation. In recent years, considerable interest has been raised towards the biological effects of environmental contaminants, particularly endocrine disrupting chemicals (EDCs). Emerging evidence suggests that prenatal exposure to selected EDCs can have a deleterious impact on the fetus and long-lasting consequences also in adult life. The results of the in vitro effects of commonly found EDCs, particularly Bisphenol A (BPA) and para-Nonylphenol (p-NP), indicate that these substances can alter hCG production and through this action could exert their fetal damage, suggesting that hCG could represent and become a potentially useful clinical biomarker of an inappropriate prenatal exposure to these substances. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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Open AccessReview Human Chorionic Gonadotropin as a Pivotal Endocrine Immune Regulator Initiating and Preserving Fetal Tolerance
Int. J. Mol. Sci. 2017, 18(10), 2166; https://doi.org/10.3390/ijms18102166
Received: 29 September 2017 / Revised: 13 October 2017 / Accepted: 16 October 2017 / Published: 17 October 2017
Cited by 5 | PDF Full-text (486 KB) | HTML Full-text | XML Full-text
Abstract
The pregnancy hormone, human chorionic gonadotropin (hCG), is crucially involved in processes such as implantation and placentation, two milestones of pregnancy whose successful progress is a prerequisite for adequate fetal growth. Moreover, hCG determines fetal fate by regulating maternal innate and adaptive immune
[...] Read more.
The pregnancy hormone, human chorionic gonadotropin (hCG), is crucially involved in processes such as implantation and placentation, two milestones of pregnancy whose successful progress is a prerequisite for adequate fetal growth. Moreover, hCG determines fetal fate by regulating maternal innate and adaptive immune responses allowing the acceptance of the foreign fetal antigens. As one of the first signals provided by the embryo to its mother, hCG has the potential to regulate very early pregnancy-driven immune responses, allowing the establishment and preservation of fetal tolerance. This mini review focuses on how hCG modulates the adaptive arm of the immune system including dendritic cells as key regulators of adaptive immune responses. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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Graphical abstract

Open AccessReview hCG: Biological Functions and Clinical Applications
Int. J. Mol. Sci. 2017, 18(10), 2037; https://doi.org/10.3390/ijms18102037
Received: 18 August 2017 / Revised: 15 September 2017 / Accepted: 19 September 2017 / Published: 22 September 2017
Cited by 5 | PDF Full-text (575 KB) | HTML Full-text | XML Full-text
Abstract
Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein
[...] Read more.
Human chorionic gonadotropin (hCG) is produced primarily by differentiated syncytiotrophoblasts, and represents a key embryonic signal that is essential for the maintenance of pregnancy. hCG can activate various signaling cascades including mothers against decapentaplegic homolog 2 (Smad2), protein kinase C (PKC), and/or protein kinase A (PKA) in several cells types by binding to luteinizing hormone/chorionic gonadotropin receptor (LHCGR) or potentially by direct/indirect interaction with transforming growth factor beta receptor (TGFβR). The molecule displays specialized roles in promoting angiogenesis in the uterine endothelium, maintaining myometrial quiescence, as well as fostering immunomodulation at the maternal-fetal interface. It is a member of the glycoprotein hormone family that includes luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and follicle-stimulating hormone (FSH). The α-subunit of hCG displays homologies with TSH, LH, and FSH, whereas the β subunit is 80–85% homologous to LH. The hCG molecule is produced by a variety of organs, exists in various forms, exerts vital biological functions, and has various clinical roles ranging from diagnosis and monitoring of pregnancy and pregnancy-related disorders to cancer surveillance. This review presents a detailed examination of hCG and its various clinical applications. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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Open AccessReview Human Chorionic Gonadotrophin as a Possible Mediator of Leiomyoma Growth during Pregnancy: Molecular Mechanisms
Int. J. Mol. Sci. 2017, 18(9), 2014; https://doi.org/10.3390/ijms18092014
Received: 29 August 2017 / Revised: 12 September 2017 / Accepted: 13 September 2017 / Published: 20 September 2017
Cited by 1 | PDF Full-text (1720 KB) | HTML Full-text | XML Full-text
Abstract
Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum
[...] Read more.
Uterine fibroids are the most common gynecologic benign tumors. Studies supporting a strong pregnancy-related growth of leiomyomas generally claimed a crucial role of sex steroid hormones. However, sex steroids are unlikely the unique actors involved as estrogen and progesterone achieve a pick serum concentration in the last trimester while leiomyomas show a typical increase during the first trimester. Given the rapid exponential raise in serum human Chorionic Gonadotrophin (hCG) at the beginning of gestation, we conducted a review to assess the potential role of hCG in the striking growth of leiomyomas during initial pregnancy. Fibroid growth during initial pregnancy seems to correlate to the similar increase of serum hCG levels until 12 weeks of gestation. The presence of functional Luteinizing Hormone/human Chorionic Gonadotropin (LH/hCG) receptors was demonstrated on leiomyomas. In vitro treatment of leiomyoma cells with hCG determines an up to 500% increase in cell number after three days. Expression of cyclin E and cyclin-dependent kinase 1 was significantly increased in leiomyoma cells by hCG treatment. Moreover, upon binding to the receptor, hCG stimulates prolactin secretion in leiomyoma cells, promoting cell proliferation via the mitogen-activated protein kinase cascade. Fibroid enlargement during initial pregnancy may be regulated by serum hCG. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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Graphical abstract

Open AccessReview Human Chorionic Gonadotropin and Breast Cancer
Int. J. Mol. Sci. 2017, 18(7), 1587; https://doi.org/10.3390/ijms18071587
Received: 13 March 2017 / Revised: 17 July 2017 / Accepted: 17 July 2017 / Published: 21 July 2017
Cited by 4 | PDF Full-text (224 KB) | HTML Full-text | XML Full-text
Abstract
Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all
[...] Read more.
Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic gonadotropin (HCG) is a candidate hormone which could mediate this antitumoral effect of pregnancy. For this review article, all original research articles on the role of HCG in breast cancer were considered, which are listed in PubMed database and were written in English. The role of HCG in breast cancer seems to be a paradox. Placental heterodimeric HCG acts as a protective agent by imprinting a permanent genomic signature of the mammary gland determining a refractory condition to malignant transformation which is characterized by cellular differentiation, apoptosis and growth inhibition. On the other hand, ectopic expression of β-HCG in various cancer entities is associated with poor prognosis due to its tumor-promoting function. Placental HCG and ectopically expressed β-HCG exert opposite effects on breast tumorigenesis. Therefore, mimicking pregnancy by treatment with HCG is suggested as a strategy for breast cancer prevention, whereas targeting β-HCG expressing tumor cells seems to be an option for breast cancer therapy. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
Open AccessReview The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence
Int. J. Mol. Sci. 2017, 18(6), 1305; https://doi.org/10.3390/ijms18061305
Received: 7 May 2017 / Revised: 12 June 2017 / Accepted: 12 June 2017 / Published: 19 June 2017
Cited by 3 | PDF Full-text (178 KB) | HTML Full-text | XML Full-text
Abstract
Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein,
[...] Read more.
Embryo implantation is a complex process involving continuous molecular cross-talk between the embryo and the decidua. One of the key molecules during this process is human chorionic gonadotropin (HCG). HCG effectively modulates several metabolic pathways within the decidua contributing to endometrial receptivity. Herein, a brief overview of the molecular mechanisms regulated by HCG is presented. Furthermore, we summarize the existing evidence regarding the clinical impact on reproductive outcomes after endometrial priming with HCG prior to embryo transfer. Although promising, further evidence is needed to clarify the protocol that would lead to beneficial outcomes. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
Open AccessReview hCG Triggering in ART: An Evolutionary Concept
Int. J. Mol. Sci. 2017, 18(5), 1075; https://doi.org/10.3390/ijms18051075
Received: 26 February 2017 / Revised: 28 April 2017 / Accepted: 6 May 2017 / Published: 17 May 2017
Cited by 2 | PDF Full-text (174 KB) | HTML Full-text | XML Full-text
Abstract
Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new
[...] Read more.
Human chorionic gonadotropin (hCG) is no longer a single, omnipotent ovulation triggering option. Gonadotropin releasing hormone (GnRH) agonist, initially presented as a substitute for hCG, has led to a new era of administering GnRH agonist followed by hCG triggering. According to this new concept, GnRH agonist enables successful ovum maturation, while hCG supports the luteal phase and pregnancy until placental shift. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
Open AccessReview Human Chorionic Gonadotropin: The Pregnancy Hormone and More
Int. J. Mol. Sci. 2017, 18(5), 1059; https://doi.org/10.3390/ijms18051059
Received: 26 February 2017 / Revised: 3 May 2017 / Accepted: 10 May 2017 / Published: 14 May 2017
Cited by 4 | PDF Full-text (184 KB) | HTML Full-text | XML Full-text
Abstract
To thoroughly review the uses of human chorionic gonadotropin (hCG) related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive
[...] Read more.
To thoroughly review the uses of human chorionic gonadotropin (hCG) related to the process of reproduction and also assess new, non-traditional theories. Review of the international literature and research studies. hCG and its receptor, LH/CGR, are expressed in numerous sites of the reproductive tract, both in gonadal and extra-goanadal tissues, promoting oocyte maturation, fertilization, implantation and early embryo development. Moreover, hCG seems to have a potential role as an anti-rejection agent in solid organ transplantation. Future research needs to focus extensively on the functions of hCG and its receptor LH/CGR, in an effort to reveal known, as well as unknown clinical potentials. Full article
(This article belongs to the Special Issue hCG—An Endocrine, Regulator of Gestation and Cancer)
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