Human chorionic gonadotrophin indirectly activates peripheral γδT cells to produce interleukin-10 during early pregnancy.

BACKGROUNDS: The immunomodulatory properties of human chorionic gonadotrophin (hCG) have been identified to be critical for successful pregnancy. However, the effects of hCG on peripheral γδT cells during early pregnancy have not been reported previously. METHODS: We cocultured the purified γδT cells and peripheral blood mononuclear cells (PBMCs) with early pregnancy-relevant hCG concentrations and investigated the changes in the immune functional characteristics of γδT cells via flow cytometry assays. RESULTS: The ratios of CD69+ and IL-10+ γδT cells were increased in early pregnant women compared to nonpregnant women. γδT cells expressed low levels of the mannose receptor (CD206) instead of the classical hCG/LH receptor for hCG. The direct treatment of purified γδT cells with early pregnancy-relevant hCG concentrations may have no significant effects on their immune functions. Interestingly, when PBMCs were treated with the same broad range of hCG concentrations, the ratios of CD69+ and IL-10+ γδT cells to total γδT cells were significantly increased. CONCLUSION: Certain early pregnancy-relevant hCG concentrations could enhance the ratios of peripheral CD69+ and IL-10+ γδT cells, contributing to the activation of γδT cells and immunological tolerance during early pregnancy. However, these affects may not be strongly mediated by direct ligand-receptor interactions and they may highly depend on immune microenvironment. Our novel observations propose a perspective into the endocrine-immune dialog that exists between the fetus and maternal immune cells.

Human chorionic gonadotropin promotes murine Treg cells and restricts pregnancy-harmful proinflammatory Th17 responses.

An equilibrium between proinflammatory and anti-inflammatory immune responses is essential for maternal tolerance of the fetus throughout gestation. To study the participation of fetal tissue-derived factors in this delicate immune balance, we analyzed the effects of human chorionic gonadotropin (hCG) on murine Treg cells and Th17 cells in vitro, and on pregnancy outcomes, fetal and placental growth, blood flow velocities and remodeling of the uterine vascular bed in vivo. Compared with untreated CD4+CD25+ T cells, hCG increased the frequency of Treg cells upon activation of the LH/CG receptor. hCG, with the involvement of IL-2, also interfered with induced differentiation of CD4+ T cells into proinflammatory Th17 cells. In already differentiated Th17 cells, hCG induced an anti-inflammatory profile. Transfer of proinflammatory Th17 cells into healthy pregnant mice promoted fetal rejection, impaired fetal growth and resulted in insufficient remodeling of uterine spiral arteries, and abnormal flow velocities. Our works show that proinflammatory Th17 cells have a negative influence on pregnancy that can be partly avoided by in vitro re-programming of proinflammatory Th17 cells with hCG.

Human Chorionic Gonadotropin-A Review of the Literature.

Importance: The measurement of human chorionic gonadotropin (hCG) levels in different body fluids is a commonly utilized tool in obstetrics and gynecology, as well as other fields. It is often one of the first steps in the medical workup of female patients, and the results and interpretation of this test can have significant downstream ramifications. It is essential to understand the uses and limitations of hCG as a testing and therapeutic measure to appropriately evaluate, counsel, and treat patients. Objective: The purpose of this article is to review the current literature on hCG, including its origins, structure, pharmacokinetics, metabolism, and utility in testing and medical treatment. Evidence Acquisition: Original research articles, review articles, and guidelines on hCG use were reviewed. Conclusions and Relevance: While the primary function of hCG is to maintain early pregnancy, testing for hCG demonstrates that this molecule is implicated in a multitude of different processes where results of testing may lead to incorrect conclusions regarding pregnancy status. This could affect patients in a myriad of settings and have profound emotional and financial consequences. In addition, hCG testing may be revealing of alternative pathology, such as malignancy. It is imperative to understand the nuances of the physiology of hCG and testing methods to effectively use and interpret this test for appropriate patient management.

Effect of ovarian stimulation by different gonadotrophin treatments on in vivo and in vitro reproductive efficiency of rabbit does under high ambient temperature.

Non-lactating multiparous NZW rabbit does (n = 227) were used in two experiments. In the 1st experiment (n = 87), does were i.m. injected with 0.1-ml saline/doe in day 0 (control, n = 29). Other does were injected with 25 IU equine chorionic gonadotrophin (eCG), followed by 0.2-ml gonadotrophin-releasing hormone (GnRH, n = 29) or 75 IU human chorionic gonadotrophin (hCG, n = 29) per doe 48 h later. After 60 h of day 0, does in all groups were artificially inseminated (AI). In the 2nd experiment, does (n = 140) were mated (AI) after synchronization of estrus/ovulation with 25 IU eCG, and 75 IU hCG 48 h later. On day 5 post-AI, does were injected with saline (control), 75 IU hCG, 0.2 ml GnRH, or 25 IU eCG per doe. Injection of eCG with GnRH or hCG pre-AI significantly increased corpora lutea number, ovulation rate, total number/doe and recovery rate of embryos, viable embryos, hatched blastocysts, in vivo reproductive parameters, and concentration of progesterone and progesterone/estradiol 17-ß ratio. Injection of eCG on day 5 post-AI significantly improved large and total follicle number, and in vivo reproductive efficiency. The corpora lutea number and impantation sites were significantly increased in the hCG and eCG groups. Fetal loss rate significantly increased only in the GnRH group. Under high ambient temperature, administration of eCG with hCG or GnRH injection pre-AI could be synchronized estrus/ovulation for improving in vivo and in vitro embryo production. In addition, pregnancy outcomes could be enhanced in rabbit does induced to ovulation by a single eCG or hCG dose on day 5 post-AI.

Gonadotrophins modulate cell death-related genes expression in human endometrium.

Background Gonadotrophins exert their functions by binding follicle-stimulating hormone receptor (FSHR) or luteinizing hormone and human chorionic gonadotropin receptor (LHCGR) present on endometrium. Within ovaries, FSH induces autophagy and apoptosis of granulosa cells leading to atresia of non-growing follicles, whereas hCG and LH have anti-apoptotic functions. Endometrial cells express functioning gonadotrophin receptors. The objective of this study was to analyze the effect of gonadotrophins on physiology and endometrial cells survival. Materials and methods Collected endometria were incubated for 48 or 72 h with 100 ng/mL of recombinant human FSH (rhFSH), recombinant human LH (rhLH) or highly purified hCG (HPhCG) alone or combined. Controls omitted gonadotrophins. The effect of gonadotrophins on cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1), hypoxia inducible factor 1α (HIF1A), and cell-death-related genes expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry for microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) and apoptotic protease activating factor 1 (APAF-1) was performed. Results Gonadotrophins are able to modulate the endometrial cells survival. FSH induced autophagy and apoptosis by increasing the relative expression of MAP1LC3B and FAS receptor. In FSH-treated samples, expression of apoptosis marker APAF-1 was detected and co-localized on autophagic cells. hCG and LH does not modulate the expression of cell-death-related genes while the up-regulation of pro-proliferative epiregulin gene was observed. When combined with FSH, hCG and LH prevent autophagy and apoptosis FSH-induced. Conclusions Different gonadotrophins specifically affect endometrial cells viability differently: FSH promotes autophagy and apoptosis while LH and hCG alone or combined with rhFSH does not.

Human Chorionic Gonadotrophin: New Pleiotropic Functions for an "Old" Hormone During Pregnancy.

Human chorionic gonadotrophin (hCG) is the first specific molecule synthesized by the embryo. hCG RNA is transcribed as early as the eight-cell stage, and the blastocyst produces the protein before its implantation. hCG in the uterine microenvironment binds with its cognate receptor, luteinizing hormone/choriogonadotropin receptor (LHCGR), on the endometrial surface. This binding stimulates leukemia inhibitory factor (LIF) production and inhibits interleukin-6 (IL-6) production by epithelial cells of the endometrium. These effects ensure essential help in the preparation of the endometrium for initial embryo implantation. hCG also effects angiogenic and immunomodulatory actions as reported in many articles by our laboratories and other ones. By stimulating angiogenesis and vasculogenesis, hCG provides the placenta with an adequate maternal blood supply and optimal embryo nutrition during the invasion of the uterine endometrium. The immunomodulatory properties of hCG are numerous and important for programming maternal immune tolerance toward the embryo. The reported effects of hCG on uterine NK, Treg, and B cells, three major cell populations for the maintenance of pregnancy, demonstrate the role of this embryonic signal as a crucial immune regulator in the course of pregnancy. Human embryo rejection for hCG-related immunological reasons has been studied in different ways, and a sufficient dose of hCG seems to be necessary to maintain maternal tolerance. Different teams have studied the addition of hCG in patients suffering from recurrent miscarriages or implantation failures. hCG could also have a beneficial or a negative impact on autoimmune diseases during pregnancy. In this review, we will discuss the immunological impacts of hCG during pregnancy and if this hormone might be used therapeutically.

Human chorionic gonadotropin and IL-35 contribute to the maintenance of peripheral immune tolerance during pregnancy through mediating the generation of IL-10+ or IL-35+ Breg cells.

Regulatory B cells (Breg cells) play critical roles in modulating immune responses during autoimmune diseases and infection. Here we explored the participation of two main Breg subsets, including IL-10+ Breg (B10) and IL-35+ Breg cells, in maintaining successful pregnancy. We first observed an elevated percentage of B10 cells in peripheral blood from first-trimester pregnant women compared with non-pregnant controls. Serum from pregnancy induced the augmentation of B10  in peripheral blood mononuclear cells from non-pregnant women. In animal models, we demonstrated that there were significant augmentation of B10 cells and obvious increase of IL-10 level in splenic B cells from normal pregnant mice compared to that in abortion-prone pregnant mice and virgin mice. Further analysis showed that both hCG and IL-35 suppressed the proliferation of mouse splenic B cells. Moreover, IL-35 induced the expansion of both mouse splenic B10 and IL-35+ Breg cells while hCG only mediated the generation of B10 cells. Subsequent study in mice demonstrated that the activation of STAT1 and STAT3 in B cells caused by IL-35 and the activation of STAT3 caused by hCG were the predominant mechanism of IL-35+ Breg and B10 cells augmentation. These findings suggested that hCG and IL-35 induced the amplification of B10 and IL-35+ Breg cells which played a vital peripheral regulatory role during pregnancy.

The gonadotropin system, lessons from animal models and clinical cases.

This review article centers upon family of gonadotropin hormones which consists of two pituitary hormones - follicle-stimulating hormone (FSH) and luteinizing hormone (LH) as well as one non-pituitary hormone - human chorionic gonadotropin (hCG) secreted by placenta, and their receptors. Gonadotropins play an essential role in proper sexual development, puberty, gametogenesis, maintenance of pregnancy and male sexual differentiation during the fetal development. They belong to the family of glycoprotein hormones thus they constitute heterodimeric proteins built of common α subunit and hormone-specific ß-subunit. Hitherto, several mutations in genes encoding both gonadotropins and their receptors have been identified in humans. Their occurrence resulted in a number of different phenotypes including delayed puberty, primary amenorrhea, hermaphroditism, infertility and hypogonadism. In order to understand the effects of mutations on the phenotype observed in affected patients, detailed molecular studies are required to map the relationship between the structure and function of gonadotropins and their receptors. Nonetheless, in vitro assays are often insufficient to understand physiology. Therefore, several animal models have been developed to unravel the physiological roles of gonadotropins and their receptors.

[The influence of chorionic gonadotropin on phenotype conversion and hTERT gene expression by T-lymphocytes of different degrees of differentiation]. / Vliianie khorionicheskogo gonadotropina na konversiiu fenotipa i ékspressiiu gena hTERT T-limfotsitami raznoi stepeni differentsirovki.

The effects of chorionic gonadotropin (hCG) on the expression of the hTERT gene in combination with the conversion of the phenotype of naive T-cells and T-cells of immune memory in vitro were studied. hCG inhibited expression of hTERT mRNA in naive T-cells (CD45RA+) and immune memory T cells (CD45RO+), causing a decrease in the replicative potential of the cells. The presence of hCG in the culture led to the conversion of the phenotype of T-lymphocytes. hCG reduced the number of proliferating T-cells of immune memory, estimated by phenotypic signs by differential gating. hCG (10 IU/ml and 100 IU/ml) inhibited expression of CD25 by the studied populations, but did not modulate expression of the CD71 proliferation marker. Thus, hCG inhibited the functional activity of naive T-cells and T-cells of immune memory, which, in the context of pregnancy, can contribute to the formation of immune tolerance to the semi-allogenic fetus.

The Role of HCG in Implantation: A Mini-Review of Molecular and Clinical Evidence.

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.

hCG Triggering in ART: An Evolutionary Concept.

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.

Human Chorionic Gonadotropin: Unknown about Known.

The last two decade discoveries shift the accent from consideration of human chorionic gonadotripin (hCG) as a hormone, that controls progesterone production by corpus luteum cells, to a powerful paracrine regulator which'in the tandem with its hyperglycozilated analog (hCG-H) induces successful implantation and coordinated dialog between blastocyst and uterus tissues. Ability of hCG to interact with TSH receptor and hCG-H with TGF-beta-RII extend significantly the spectrum of processes controlled by these molecules. Differences between intracellular pathways of signal transduction between hCG and LH mediated by the same receptor (LH/hCG-R) impugn unity of their effector mechanisms previously considered as obvious. Paracine properties-of hCG comprise control of fusing of trophoblasts into syncytiotrophoblasts, angiogenesis, immunity regulation and endometrium predisposition to implantation. Angiogenesis is associated with LH/hCG-R expressed on mural cells of uterine spiral arteries as well as induced secretion of soluble VEGF type by endometrial cells. hCG.regulates ratio between different forms of T-helper cells in maternal organism on the initial gestation stage determining high level of Th2 cells. hCG supports local immunotolerance acting as chemoattractant for T-suppressors (T-Treg) and apoptotic factor for T-lymphocytes. Endometrial susceptibility arises from activation of osteopantin secretion and decline of mucin secretion by epithelial cells. hCG-H acts on the same tissues as hCG as a paracrine agent regulating multiple cascades of cytokines. hCG-H plays the key role in trophoblast invasion into,uterine decidua as a result of gelatinase secretion by these cells.The degree of angiogenic effect of hCG-H is compatiblewith hCG but its signal transduction is mediated by TGF-beta signal transduction pathway that stimulates mural cell proliferation. hCG-H acts as mitogen on NK-cells and is able to activate them and direct to angiogenesis maintenance. In this article the attempt was made to elucidate the most important discoveries about the role of hCG and its hyperglycosylated analog yet accomplished and still upcoming.

Human chorionic gonadotropin: Different glycoforms and biological activity depending on its source of production.

Human chorionic gonadotropin (hCG) is the first hormonal message from the placenta to the mother. It is detectable in maternal blood two days after implantation and behaves like a super LH agonist stimulating progesterone secretion by the corpus luteum. In addition to maintaining the production of progesterone until the placenta itself produces it, hCG also has a role in myometrial quiescence and local immune tolerance. Specific to humans, hCG is a complex glycoprotein composed of two highly glycosylated subunits. The α-subunit is identical to the pituitary gonadotropin hormones (LH, FSH, TSH), contains two N-glycosylation sites, and is encoded by a single gene (CGA). By contrast, the ß-subunits are distinct for each hormones and confer both receptor and biological specificity, although LH and hCG bind to the same receptor (LH/CG-R). The hCG ß-subunit is encoded by a cluster of genes (CGB) and contains two sites of N-glycosylation and four sites of O-glycosylation. The hCG glycosylation state varies with the stage of pregnancy, its source of production and in the pathology. It is well established that hCG is mainly secreted into maternal blood, where it peaks at 8-10weeks of gestation (WG), by the syncytiotrophoblast (ST), which represents the endocrine tissue of the human placenta. The invasive extravillous trophoblast (iEVT) also secretes hCG, and in particular hyperglycosylated forms of hCG (hCG-H) also produced by choriocarcinoma cells. In maternal blood, hCG-H is elevated during early first trimester corresponding to the trophoblastic cell invasion process and then decreases. In addition to its endocrine role, hCG has autocrine and paracrine roles. It promotes formation of the ST and angiogenesis through LH/CG-R but has no effect on trophoblast invasion in vitro. By contrast, hCG-H stimulates trophoblast invasion and angiogenesis by interacting with the TGFß receptor in a LH/CG-R independent signalling pathway. hCG is largely used in antenatal screening and hCG-H might represent a serum marker of implantation and early trophoblast invasion. In conclusion, hCG is the major pregnancy glycoprotein hormone, whose maternal concentration and glycan structure change all along pregnancy. Depending on its source of production, glycoforms of hCG display different biological activities and functions that are essential for pregnancy outcome.

The controversial role of human chorionic gonadotropin in the development of breast cancer and other types of tumors.

INTRODUCTION: Breast cancer is the most often diagnosed tumor of women and one of the leading cause of cancer related death. Due to different known risk factors there are epidemiological differences. Beside genetic disorders and patient's age it is especially the age of the first full-term pregnancy and in this context the pregnancy hormone human chorionic gonadotropin that seems to play an important role. METHODS: This review is based on a PubMed research in publications of the last 20 years. Only articles in English language were considered. RESULTS: The effect of human chorionic gonadotropin on development of cancer is controversial. In fact, for breast cancer there is evidence that this hormone has a protective effect against tumorigenesis due the differentiation of the mammary tissue after a full term pregnancy through the downregulation of estrogen receptors. CONCLUSION: Human chorionic gonadotropin has among promoting pregnancy important controversial functions especially in tumor development. The mechanisms that explain the pro- and anti-carcinogenic effects are not fully understood yet. It seems to have a protective effect on breast cancer through increasing differentiation and hereby decreasing susceptibility of the mammary tissue for toxicants. This knowledge might help developing a preventive agent in the next future that uses the anti-carcinogenic effect of human chorionic gonadotropin and thereby decrease the mortality out of breast cancer.

Gonadotropins facilitate potential differentiation of human bone marrow mesenchymal stem cells into Leydig cells in vitro.

Infertility due to low testosterone levels has increased in recent years. This has impacted the social well-being of the patients. This study was undertaken to investigate the potential of gonadotropins in facilitating differentiation of human bone marrow mesenchymal stem cells (BMSCs) into Leydig cells in vitro. BMSCs were isolated, cultured, and their biological characteristics were observed. BMSCs were induced with gonadotropins in vitro and their ability to differentiate into Leydig cells was studied. The level of expression of 3-beta hydroxysteroid dehydrogenase (3ß-HSD) and secretion of testosterone were determined using flow cytometry and enzyme-linked immunosorbent assay, respectively, and the results were compared between the experimental and control groups. The cultured BMSCs showed a typical morphology of the fibroblast-like colony. The growth curve of cells formed an S-shape. After inducing the cells for 8-13 days, the cells in the experimental group increased in size and showed typical characteristics of Leydig cells, and the growth occurred in spindle or stellate shapes. Cells from the experimental group highly expressed 3ß-HSD, and there was a gradual increase in the number of Leydig cells. The control group did not express 3ß-HSD. The level of testosterone in the experimental group was higher than the control group (p < 0.05). Additionally, the cells in the experimental group secreted higher levels of testosterone with increased culture time. The expression of Leydig cell-specific markers in the experimental group was significantly higher (p < 0.05). With these findings, BMSCs can be considered a new approach for the treatment of patients with low androgen levels.

[The Influence of Chorionic Gonadotropin and Estriol on NK Cells Phenotype and Functional Activity.]

The influence of chorionic gonadotropin (CG) and estriol (E3) at concentrations typical of pregnancy on the expression of phenotypic markers and cytokine production by separated NK cells were studied. It is found that these hormones increase the percentage of CD56brightL-selectin+ NK-cells, but also stimulate the expression of the inhibitory molecule NKG2A in the lymphocytes. In addition, E3 and CG stimulate the production of TGF-B, inhibiting the secretion of all other cytokines by separated NK cells. In general, these hor- mones contribute to the formation of the phenotype and cytokine spectrum characteristic of the regulatory NK3 subpopulation of NK cells during pregnancy.

Establishment and evaluation of a stable steroidogenic goat Leydig cell line.

Leydig cells play a key role in synthesizing androgen and regulating spermatogenesis. The dysfunction of Leydig cells may lead to various male diseases. Although primary Leydig cell cultures have been used, their finite lifespan hinders the assessment of long-term effects. In the present study, primary goat Leydig cells (GLCs) were immortalized via the transfection of a plasmid containing the human telomerase reverse transcriptase (hTERT) gene. The expressions of hTERT and telomerase activity were evaluated in transduced GLCs (hTERT-GLCs). These cells steadily expressed the hTERT gene and exhibited longer telomere lengths at passage 55 that were similar to those of HeLa cells. The hTERT-GLCs at passages 30 and 50 expressed genes that encoded key proteins, enzymes and receptors that are inherent to normal Leydig cells, for example, steroidogenic acute regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and LH-receptor (LH-R). Additionally, the immortalized goat Leydig cells secreted detectable quantities of testosterone in response to hCG stimulation. Furthermore, this cell line appeared to proliferate more quickly than the control cells, although no neoplastic transformation occurred in vitro. We concluded that the GLCs immortalized with hTERT retained their original characteristics and might provide a useful model for the study of Leydig cell function.

The endocrine function of human placenta: an overview.

During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications. In fact, altered levels of these hormones have been associated with some pathologies, such as chromosomal anomalies or pre-eclampsia. This review proposes to revise and update the main pregnancy-related hormones, addressing their major characteristics, molecular targets, function throughout pregnancy, regulators of their expression and their potential clinical interest.

A case study on the potential angiogenic effect of human chorionic gonadotropin hormone in rapid progression and spontaneous regression of metastatic renal cell carcinoma during pregnancy and after surgical abortion.

BACKGROUND: Treatment possibilities of metastatic renal cell carcinoma (mRCC) have recently changed dramatically prolonging the overall survival of the patients. This kind of development brings new challenges for the care of mRCC. CASE PRESENTATION: A 22 year-old female patient with translocation type mRCC, who previously had been treated for nearly 5 years, became pregnant during the treatment break period. Follow-up examinations revealed a dramatic clinical and radiological progression of mRCC in a few weeks therefore the pregnancy was terminated. A few days after surgical abortion, CT examination showed a significant spontaneous regression of the pulmonary metastases, and the volume of the largest manifestation decreased from ca. 30 to 3.5 cm(3) in a week. To understand the possible mechanism of this spectacular regression, estrogen, progesterone and luteinizing hormone receptors (ER, PGR and LHR, respectively) immuno-histochemistry assays were performed on the original surgery samples. Immuno-histochemistry showed negative ER, PGR and positive LHR status suggesting the possible angiogenic effect of human chorionic gonadotropin hormone (hCG) in the background. CONCLUSION: We hypothesize that pregnancy may play a causal role in the progression of mRCC via the excess amount of hCG, however, more data are necessary to validate the present notions and the predictive role of LHR overexpression.

The Role of Human Chorionic Gonadotropin as Tumor Marker: Biochemical and Clinical Aspects.

Tumor markers are biological substances that are produced/released mainly by malignant tumor cells, enter the circulation in detectable amounts and are potential indicators of the presence of a tumor. The most useful biochemical markers are the tumor-specific molecules, i.e., receptors, enzymes, hormones, growth factors or biological response modifiers that are specifically produced by tumor cells and not, or minimally, by the normal counterpart (Richard et al. Principles and practice of gynecologic oncology. Wolters Kluwer Health, Philadelphia, 2009). Based on their specificity and sensitivity in each malignancy, biomarkers are used for screening, diagnosis, disease monitoring and therapeutic response assessment in clinical management of cancer patients.This chapter is focused on human chorionic gonadotropin (hCG), a hormone with a variety of functions and widely used as a tumor biomarker in selected tumors. Indeed, hCG is expressed by both trophoblastic and non-trophoblastic human malignancies and plays a role in cell transformation, angiogenesis, metastatization, and immune escape, all process central to cancer progression. Of note, hCG testing is crucial for the clinical management of placental trophoblastic malignancies and germ cell tumors of the testis and the ovary. Furthermore, the production of hCG by tumor cells is accompanied by varying degrees of release of the free subunits into the circulation, and this is relevant for the management of cancer patients (Triozzi PL, Stevens VC, Oncol Rep 6(1):7-17, 1999).The name chorionic gonadotropin was conceived: chorion derives from the latin chordate meaning afterbirth, gonadotropin indicates that the hormone is a gonadotropic molecule, acting on the ovaries and promoting steroid production (Cole LA, Int J Endocrinol Metab 9(2):335-352, 2011). The function, the mechanism of action and the interaction between hCG and its receptor continue to be the subject of intensive investigation, even though many issues about hCG have been well documented (Tegoni M et al., J Mol Biol 289(5):1375-1385, 1999).