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International Journal of Molecular... May 2018Human Chorionic Gonadotropin (hCG) is a heterodimeric glycoprotein composed of two subunits [...].
Human Chorionic Gonadotropin (hCG) is a heterodimeric glycoprotein composed of two subunits [...].
Topics: Chorionic Gonadotropin; Disease Susceptibility; Endocrine System; Female; Humans; Neoplasms; Pregnancy; Reproductive Physiological Phenomena
PubMed: 29772831
DOI: 10.3390/ijms19051502 -
International Journal of Molecular... Jul 2017Breast cancer is well known as a malignancy being strongly influenced by female steroids. Pregnancy is a protective factor against breast cancer. Human chorionic... (Review)
Review
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.
Topics: Apoptosis; Breast Neoplasms; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Genomic Imprinting; Humans; Placenta; Pregnancy
PubMed: 28754015
DOI: 10.3390/ijms18071587 -
The Yale Journal of Biology and Medicine 1991Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits, alpha and beta. Nicks or missing peptide linkages have been found in... (Review)
Review
Human chorionic gonadotropin (hCG) is a glycoprotein hormone composed of two dissimilar subunits, alpha and beta. Nicks or missing peptide linkages have been found in the beta 44-52 region of the beta-subunit of hCG, whether from pregnancy or trophoblast disease. This article reviews recent reports about the location of nicks in hCG, their origin and occurrence, their effects on the steroidogenic and receptor-binding activities of hCG, and on the immunological activities of hCG and its free beta-subunit. Taken together, the reports show: (1) nicks occur primarily between beta 47 and beta 48, and to a lesser extent between beta 44 and beta 45; (2) the extent of nicking in hCG samples varies widely, from undetectable to 100 percent of molecules; (3) nicks greatly reduce the steroidogenic activity of hCG in vitro (nicked molecules have less than 20 percent of the activity of the intact hormone); (4) nicks may occur at the trophoblast-myometrial interface or in the circulation by the action of human leucocyte elastase or similar leucocytic protease; (5) hCG testing kits using dimer-specific antibodies may not detect nicked molecules and may give different results from those using other antibodies; (6) hCG international reference preparations and the CR series of hCG standards are variably nicked (10 percent to 20 percent), complicating the problem of discordant hCG results in nick-sensitive assays; (7) results from commonly used immunoassays for measurement of the hCG free beta-subunit vary by as much as tenfold because some of the antibodies employed do not detect nick free beta-subunit.
Topics: Amino Acid Sequence; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Female; Humans; Immunoassay; Molecular Sequence Data; Peptide Fragments; Pregnancy; Trophoblastic Neoplasms; Uterine Neoplasms
PubMed: 1725683
DOI: No ID Found -
Frontiers in Immunology 2022An equilibrium between proinflammatory and anti-inflammatory immune responses is essential for maternal tolerance of the fetus throughout gestation. To study the...
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 , and on pregnancy outcomes, fetal and placental growth, blood flow velocities and remodeling of the uterine vascular bed . Compared with untreated CD4CD25 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 re-programming of proinflammatory Th17 cells with hCG.
Topics: Animals; Chorionic Gonadotropin; Female; Humans; Interleukin-2; Mice; Placenta; Pregnancy; T-Lymphocytes, Regulatory; Th17 Cells
PubMed: 36203576
DOI: 10.3389/fimmu.2022.989247 -
Frontiers in Immunology 2019Human chorionic gonadotropin (hCG) serves as one of the first signals provided by the embryo to the mother. Exactly at the time when the first step of the implantation... (Review)
Review
Human chorionic gonadotropin (hCG) serves as one of the first signals provided by the embryo to the mother. Exactly at the time when the first step of the implantation process is initiated and the blastocyst adheres to the maternal endometrium, the embryonic tissue starts to actively secrete hCG. Shortly thereafter, the hormone can be detected in the maternal circulation where its concentration steadily increases throughout early pregnancy as it is continuously released by the forming placenta. Accumulating evidence underlines the critical function of hCG for embryo implantation and placentation. hCG not only regulates biological aspects of these early pregnancy events but also supports maternal immune cells in their function as helpers in the establishment of an adequate embryo-endometrial relationship. In view of its early presence in the maternal circulation, hCG has the potential to influence both local uterine immune cell populations as well as peripheral ones. The current review aims to summarize recent literature on the participation of innate and adaptive immune cells in embryo implantation and placentation with a specific focus on their regulation by hCG.
Topics: Chorionic Gonadotropin; Embryo Implantation; Embryonic Development; Female; Humans; Immunity; Placentation; Pregnancy
PubMed: 31921157
DOI: 10.3389/fimmu.2019.02896 -
Reviews in Endocrine & Metabolic... Dec 2011The primary embryonic signal in primates is chorionic gonadotropin (CG, designated hCG in humans), that is classically associated with corpus luteum rescue and... (Review)
Review
The primary embryonic signal in primates is chorionic gonadotropin (CG, designated hCG in humans), that is classically associated with corpus luteum rescue and progesterone production. However, research over the past decade has revealed the presence of the hCG receptor in a variety of extragonadal tissues. Additionally, discoveries of the multiple variants of hCG, namely, native hCG, hyperglycosylated hCG (hyp-hCG) and the β- subunit of the hyperglycosylated hCG (hCG-free β) has established a role for extragonadal actions of hCG. For the initiation and maintenance of pregnancy, hCG mediates multiple placental, uterine and fetal functions. Some of these include development of syncytiotrophoblast cells, mitotic growth and differentiation of the endometrium, localized suppression of the maternal immune system, modulation of uterine morphology and gene expression and coordination of intricate signal transduction between the endometrium. Recurrent pregnancy loss, pre-eclampsia and endometriosis are associated with altered responses of hCG, all of which have a detrimental effect on pregnancy. A role for hyp-hCG in mediating the development of both trophoblastic and non-trophoblastic tumors has also been suggested. Other significant non-gonadal applications of hCG include predicting preeclampsia, determining the risk of Down's syndrome and gestational trophoblastic disease, along with relaxing myometrial contractility and preventing recurrent miscarriages. Presence of hCG free-β in serum of cancer patients enables its usage as a diagnostic tumor marker. Thus, the extragonadal functions of hCG encompasses a wide spectrum of applications and is an open area for continued investigation.
Topics: Animals; Chorionic Gonadotropin; Female; Gonads; Humans; Models, Biological; Pregnancy; Pregnancy Tests; Signal Transduction
PubMed: 21845366
DOI: 10.1007/s11154-011-9193-1 -
Fertility and Sterility Apr 2015A single bolus of human chorionic gonadotropin (hCG) at midcycle has been the gold standard for triggering final oocyte maturation and ovulation in assisted reproductive... (Review)
Review
A single bolus of human chorionic gonadotropin (hCG) at midcycle has been the gold standard for triggering final oocyte maturation and ovulation in assisted reproductive technology cycles. More recently, gonadotropin-releasing hormone (GnRH)-agonist (GnRH-a) triggering has been introduced. The GnRH-a trigger may allow a more physiologic surge of both luteinizing hormone (LH) and follicle-stimulating hormone, although whether the combined surge will result in improved oocyte and embryo quality remains to be seen. However, the short duration of the LH surge with the GnRH-a trigger (approximately 34 hours) has been shown to be beneficial for preventing ovarian hyperstimulation syndrome in GnRH antagonist in vitro fertilization (IVF) cycles when compared with the prolonged elevation of hCG (≥6 days) after exposure to an hCG bolus. This review discusses the physiologic basis for the use of a GnRH-a trigger in IVF cycles.
Topics: Chorionic Gonadotropin; Female; Fertility Agents, Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Ovarian Hyperstimulation Syndrome; Ovulation Induction; Pregnancy; Pregnancy Rate
PubMed: 25712575
DOI: 10.1016/j.fertnstert.2014.12.129 -
Journal of Assisted Reproduction and... Jul 2007Failed implantation is a major limiting factor in infertility and early pregnancy loss. In primates, human chorionic gonadotropin mediated inhibition of stromal cell... (Review)
Review
PURPOSE
Failed implantation is a major limiting factor in infertility and early pregnancy loss. In primates, human chorionic gonadotropin mediated inhibition of stromal cell apoptosis and their subsequent differentiation into decidual cells is critical for successful embryo implantation. A major regulator of cell survival and differentiation is the Notch receptor, which transduces extracellular signals responsible for cell fate determination during development. Proteolytic cleavage of full-length Notch1 releases an active intracellular peptide, which later translocates to the nucleus and activates gene transcription. Induction of Notch1 during the window of uterine receptivity in stromal fibroblasts in response to chorionic gonadotropin upregulates anti- apoptotic genes and induces alpha-smooth muscle actin, enabling stromal cells to proliferate and differentiate into a decidualized phenotype. As such, prior to implantation the embryonic signal, chorionic gonadotropin, rescues stromal fibroblasts from normal regression at the end of each ovarian cycle.
CONCLUSION
We are suggesting that chorionic gonadotropin and Notch1 coordinately regulate decidualization by preventing apoptosis of endometrial stromal fibroblasts, averting uterine sloughing, and promoting cell survival and differentiation into the decidualized phenotype, which is critical for the maintenance of pregnancy.
Topics: Apoptosis; Chorionic Gonadotropin; Embryo Implantation; Endometrium; Female; Humans; Pregnancy; Receptor, Notch1; Stromal Cells
PubMed: 17616802
DOI: 10.1007/s10815-007-9149-2 -
Frontiers in Immunology 2021Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory... (Review)
Review
Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources ("cytokine storm"). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.
Topics: Animals; Anti-Inflammatory Agents; Bacteria; Chorionic Gonadotropin; Cytokine Release Syndrome; Glycoproteins; Humans; Inflammation; Peptides; Sepsis
PubMed: 34589085
DOI: 10.3389/fimmu.2021.714177 -
International Journal of Molecular... May 2023The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the...
The equine chorionic girdle is comprised of specialized invasive trophoblast cells that begin formation approximately 25 days after ovulation (day 0) and invade the endometrium to become endometrial cups. These specialized trophoblast cells transition from uninucleate to differentiated binucleate trophoblast cells that secrete the glycoprotein hormone equine chorionic gonadotropin (eCG; formerly known as pregnant mare serum gonadotropin or PMSG). This eCG has LH-like activity in the horse but variable LH- and FSH-like activity in other species and has been utilized for these properties both in vivo and in vitro. To produce eCG commercially, large volumes of whole blood must be collected from pregnant mares, which negatively impacts equine welfare due to repeated blood collections and the birth of an unwanted foal. Attempts to produce eCG in vitro using long-term culture of chorionic girdle explants have not been successful beyond 180 days, with peak eCG production at 30 days of culture. Organoids are three-dimensional cell clusters that self-organize and can remain genetically and phenotypically stable throughout long-term culture (i.e., months). Human trophoblast organoids have been reported to successfully produce human chorionic gonadotropin (hCG) and proliferate long-term (>1 year). The objective of this study was to evaluate whether organoids derived from equine chorionic girdle maintain physiological functionality. Here we show generation of chorionic girdle organoids for the first time and demonstrate in vitro production of eCG for up to 6 weeks in culture. Therefore, equine chorionic girdle organoids provide a physiologically representative 3D in vitro model for chorionic girdle development of early equine pregnancy.
Topics: Pregnancy; Humans; Horses; Animals; Female; Gonadotropins, Equine; Cell Differentiation; Trophoblasts; Chorionic Gonadotropin; Organoids
PubMed: 37298490
DOI: 10.3390/ijms24119538