hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, ...hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary.
hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
hCG, the wonder of today's science Cole, Laurence A
Reproductive biology and endocrinology,
03/2012, Letnik:
10, Številka:
1
Journal Article
Recenzirano
Odprti dostop
hCG is a wonder. Firstly, because hCG is such an extreme molecule. hCG is the most acidic glycoprotein containing the highest proportion of sugars. Secondly, hCG exists in 5 common forms. Finally, it ...has so many functions ranging from control of human pregnancy to human cancer. This review examines these molecules in detail.
These 5 molecules, hCG, sulfated hCG, hyperglycosylated hCG, hCG free beta and hyperglycosylated free beta are produced by placental syncytiotrophoblast cells and pituitary gonadotrope cells (group 1), and by placental cytotrophoblast cells and human malignancies (group 2). Group 1 molecules are both hormones that act on the hCG/LH receptor. These molecules are central to human menstrual cycle and human pregnancy. Group 2 molecules are autocrines, that act by antagonizing a TGF beta receptor. These molecules are critical to all advanced malignancies.
The hCG groups are molecules critical to both the molecules of pregnancy or human life, and to the advancement of cancer, or human death.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH), hCG exists in ...multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta). This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent gestational trophoblastic disease, diagnosing placental site trophoblastic tumor, managing testicular germ cell malignancies, and monitoring other human malignancies. There are very few molecules with such wide and varying functions as regular hCG and its variants, and very few tests with such a wide spectrum of clinical applications as total hCG.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The hCG amino acid sequence supports 5 glycoproteins. All are called hCG forms. This review examines all 5 molecules, the hormone as produced by the placental syncytiotrophoblast cells, the sulfated ...hormone produced by the pituitary gonadotrope cells, the hyperglycosylated hCG autocrine made by placental cytotrophoblast cells, and the autocrine cancer promoters hyperglycosylated hCG, hCGß and hyperglycosylated hCGß as made by all malignancies. This review examines all the molecules and multiple proven functions, ranging from evolution to cancer promotion to hormone action.
hCG forms are critical super-growth factors in humans, with an exceptional wide range of functions.
► This paper reviews every aspect of 5 variants of hCG. ► The biological function and detection of hCG are examined. ► The paper examines the structure, biological function and detection of hyperglycosylated hCG. ► The biological functions of sulfated hCG are examined and functions during the menstrual cycle. ► The function of hCGß and hyperglycosylated hCGß, two cancer promoters, is investigated.
► This article examines and shows that Hyperglycosylated hCG, Hyperglycosylated hCGβ and hCGβ are interchangeable in choriocarcinoma, bladder and endometrial cancer. ► Hyperglycosylated hCG, hCGβ and ...Hyperglycosylated hCGβ may all function at TGFβ antagonists. ► hCG has no inter-relatable activity. ► Hyperglycosylated hCG, hCGβ and Hyperglycosylated hCGβ are inter-relatable cancer promoters.
Several groups are researching cancers, and showing that hCGβ is a promoter of cancer growth and malignancy. Recent research shows that some hCGβ is present as Hyperglycosylated hCGβ. Other groups studied Hyperglycosylated hCG as a promoter of choriocarcinoma and germ cell malignancies. The question therefore arises, are Hyperglycosylated hCG, hCGβ and Hyperglycosylated hCGβ interrelated or interchangable promoters of cancer?
The actions of Hyperglycosylated hCGβ, hCGβ and Hyperglycosylated hCG are investigated in 7 cell lines, Jar and JEG-3 choriocarcinoma cell lines, NTERA germ cell cancer line, SCaBER and T24 bladder epithelial carcinoma lines, KLE and Hec-1-a endometrial adenocarcinoma and epithelial carcinoma cell lines. Actions of promoters on cell growth are investigated.
The actions of Hyperglycosylated hCG, hCGβ and Hyperglycosylated hCGβ appear to be interchangeable in all cell lines investigated.
All hCG-related cancer promoters seem interrelated, working through a similar mechanism, antagonism of apoptosis through know receptors such as TGFβ receptors in all cancers studied.
Abstract Considerable evidence indicates that one third of early pregnancy failures, spontaneous abortions and biochemical pregnancies, are due to chromosomal abnormalities, and two thirds are due to ...inappropriate implantation. These findings led us to investigate the role of hyperglycosylated hCG, an important pregnancy implantation signal, in pregnancy failures. We used urinary hCG determinations to evaluate a total of 127 pregnancies on the day of implantation, as marked by a positive urinary hCG. These included 81 normal term pregnancies, 18 spontaneous abortion pregnancies, and 28 biochemical pregnancies. Of the normal term pregnancies, the mean ± standard deviation concentration of hyperglycosylated hCG was 5.4 ± 4.3 mIU/ml equivalents, and the percentage of hyperglycosylated hCG was 88 ± 17%. All term pregnancies produced hyperglycosylated hCG > 51%. Of the 18 cases that spontaneously aborted, both the mean hyperglycosylated hCG (1.9 ± 2.0 mIU/ml equivalents) and the percentage of hyperglycosylated hCG (41 ± 33%) were significantly lower than in the normal pregnancy group. Only 4/18 spontaneously aborting pregnancies produced more than 51% hyperglycosylated hCG on the day of implantation. Similarly, of the 28 biochemical pregnancies, both the mean hyperglycosylated hCG (0.63 ± 1.3 mIU/ml equivalents) and the percentage of hyperglycosylated hCG (21 ± 29%) were significantly lower than in the normal pregnancy group. Only 4/28 pregnancies produced more than 51% hyperglycosylated hCG. Low hyperglycosylated hCG concentrations are associated with pregnancy failure. Whether this association is a primary cause of pregnancy failure or is simply a marker for an abnormal conceptus requires further investigation.
Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) is a neurodegenerative disease marked by early-onset cataract and hearing loss, retinitis pigmentosa, and involvement ...of both the central and peripheral nervous systems, including demyelinating sensorimotor polyneuropathy and cerebellar ataxia. Previously, we mapped this Refsum-like disorder to a 16 Mb region on chromosome 20. Here we report that mutations in the ABHD12 gene cause PHARC disease and we describe the clinical manifestations in a total of 19 patients from four different countries. The ABHD12 enzyme was recently shown to hydrolyze 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors CB1 and CB2. Our data therefore represent an example of an inherited disorder related to endocannabinoid metabolism. The endocannabinoid system is involved in a wide range of physiological processes including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation, and several potential drugs targeting these pathways are in development for clinical applications. Our findings show that ABHD12 performs essential functions in both the central and peripheral nervous systems and the eye. Any future drug-mediated interference with this enzyme should consider the potential risk of long-term adverse effects.
The hCG assay or pregnancy test Cole, Laurence A.
Clinical chemistry and laboratory medicine,
04/2012, Letnik:
50, Številka:
4
Journal Article
Recenzirano
This review examines human chorionic gonadotropin (hCG) or pregnancy tests from multiple perspectives. It first investigates the molecule hCG and shows that the term represents five independent ...molecules differing in carbohydrate and meric structure that share a common amino acid sequence. The review goes on to show that multiple degradation produces also the need to be tested for an hCG or pregnancy test to be optimally efficient. The review then carefully examines the literature showing the sensitivity and specificity of automated laboratory tests. Point-of-care pregnancy tests are then investigated along with over-the-counter pregnancy tests. Appropriate detection of hyperglycosylated hCG, nicked hCG, nicked hCG missing the β-subunit C-terminal peptide and nicked hyperglycosylated hCG is a limitation on all pregnancy tests. In the opinion of the author, just one automated laboratory test, the Siemen’s Immulite, one point-of-care test, the Beckman-Coulter Icon 25, and one brand of over-the-counter device, First Response, are suitable for early pregnancy detection and possibly other applications.
The normal variabilities of the menstrual cycle Cole, Laurence A., Ph.D; Ladner, Donald G., M.D; Byrn, Francis W., M.D
Fertility and sterility,
02/2009, Letnik:
91, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Objective To address conflicts in the normal variabilities of the menstrual cycle using the newest generation test methods and to establish normal ranges for use in clinical practice. Design Daily ...urine samples were collected from 167 women eager to achieve pregnancy. Samples were tested prospectively for LH and total hCG. A total of 458 nongestational and 111 gestational menstrual cycles were evaluated. Setting Division of Women's Health Research, University of New Mexico. Patient(s) One hundred sixty-seven women desiring pregnancy. Intervention(s) None. Main Outcome Measure(s) Levels of hCG and LH. Result(s) Menstrual cycles were 27.7 ± 2.4 days in length. The LH peak indicated the onset of the presumed ovulatory window, which occurs at 14.7 ± 2.4 days. Implantation (first day of sensitive detection of hCG) occurred in gestational menstrual cycles at 24.6 ± 3.1 days, or 4.3 ± 2.2 days before missing the expected onset of menses. Conclusion(s) Our data confirm epidemiological studies on menstrual cycle length and variability and hormonal studies on timing of the ovulatory window and its variability. They dispute, however, the published data on the timing and variance of implantation. As shown, implantation is limited to a 10-day interval culminating in the day of the expected onset of menses. Reference range data provide guidelines for differentiating normal and problem menstrual cycles.
Objective To investigate the proportion of hyperglycosylated human chorionic gonadotropin (hCG-H) produced at the time of implantation as a predictor of pregnancy success. Design Measuring daily ...urine hCG and hCG-H on the day of implantation. The time of implantation was assumed to be the first day of hCG detection (total hCG >1 mIU/mL). Setting Urine samples were collected at volunteers' homes throughout city of Albuquerque. Patient(s) 110 women attempting to conceive spontaneously; 62 achieved pregnancies (42 to term and 20 failed). Intervention(s) None. Main Outcome Measure(s) Measurements of the total hCG and hCG-H, and calculations of the proportion of hCG-H. Result(s) In all 42 term pregnancies, the proportion of hCG-H on the day of implantation was >50%. This was also true for 7 of the 20 failures. Statistically significant lower proportions of hCG-H (<50%) were observed in 13 of 20 pregnancies that eventually failed. The predictive values of proportion of hCG-H, concentration of hCG-H, total hCG, and regular hCG alone for detecting failures were 100%, 59%, 41%, and 21%, respectively. Conclusion(s) Hyperglycosylated is produced by cytotrophoblast cells in early pregnancy at the time of implantation. Effective proportions of hCG-H (>50%) are required for successful growth and invasion by cytotrophoblasts at the time of implantation. Low proportions of hCG-H at implantation predict failure and are likely to be the root of many pregnancy failures. The 7 of 20 failures with normal proportions of hCG-H were likely due to genetic, immune, or maternal causes. Measurement of a proportion of hCG-H <50% on the day of implantation absolutely indicates a failing pregnancy.
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