Most observations suggest that hCG has an inhibitory or suppressive function on macrophage activity. One group, Wan et al. It has been indicated by two groups that uterine growth in line with fetal growth may be stimulated by hCG, so that the uterus expands with fetal size during pregnancy [ 39 , 40 ] Table 1. Four groups have shown that hCG relaxes myometrial contractions during the course of pregnancy. It has been suggested that this drop may be the cause of increased contractions in the weeks prior to delivery.
Goldsmith et al. Rao et al. It is suggested that hCG may promote organ growth and differentiation in the fetus. The human fetus might produce its own hCG from the kidneys and liver [ 44 , 50 ].
The concentrations of hCG in the fetal circulation, however, are much lower than maternal concentrations, suggesting that placental hCG secretion is directed towards the maternal circulation and it is prevented from entering into fetal circulation [ 50 ]. As such, all the findings regarding the fetus have to be considered as just suggestions at this time. Unfortunately, all animals except advanced primates do not make a form of hCG, making the role of hCG in the fetus difficult to confirm.
It is interesting that hCG and hyperglycosylated hCG work together to promote the growth growth of root cytotrophoblast cells, hyperglycosylated hCG and differentiation promoted by hCG of the placenta, and promotion of the uterine blood supply to meet the invading placenta promoted by hCG.
The next step is the development of the umbilical cord and circulation. This is also seemingly promoted by hCG, suggesting hCG and hyperglycosylated hCG involvement in multiple steps of placentation and fetal development [ 44 — 49 , 51 — 53 ]. Multiple publications suggest a signaling occurs between the unimplanted blastocyst and the decidua tissue [ 54 — 57 ]. In response, the endometrium is prepared for an impending implantation [ 54 — 57 ]. These non-vascular communications by hCG are a critical part of successful pregnancy.
Recent studies show the importance of a receptive endometrium and of hCG preimplantation signaling in a successful pregnancy [ 58 — 60 ]. Other new data shows other pre-pregnancy implantation function of hCG. Publications from Rao et al. It possibly has some relationship to fertility. It has long been speculated that hCG may have a role in implantation of pregnancy [ 64 — 67 ].
Publications suggest an autocrine or paracrine function of hCG in implantation of pregnancy. However, hCG is an endocrine. We now know from recent research that a variant of hCG, hyperglycosylated hCG, rather than hCG itself, is produced by cytotrophoblast cells [ 6 , 7 ]. Hyperglycosylated hCG is an autocrine or paracrine and has been shown to directly promote implantation of pregnancy [ 6 , 8 , 9 ].
This is seeming what was considered the hCG implantation function. Hyperglycosylated hCG and its role in implantation of pregnancy are reviewed in Section 3. A recent study by Fluhr and collages [ 65 ], suggest a direct role of hCG in cytotrophoblast cell metalloproteinase production, this could be true and needs careful investigation.
CNS receptors are present in several areas of the brain such as the hippocampus, hypothalamus and brain stem [ 68 , 69 ] Table 1. The finding of an hCG receptor in these parts of the brain may explain the hyperemesis gravidarum or nausea and vomiting that occurs during normal pregnancy.
They seemingly start their action early with blastocyst signaling of the endometrium of forthcoming implantation. Hyperglycosylated hCG then promotes implantation and growth of cytotrophoblast cells. During this time hCG acts on the maternal brain to promote hyperemesis gravidarum. Taking everything together, hCG and hyperglycosylated hCG are the hormone and autocrine that seemingly control pregnancy. Hyperglycosylated hCG is a glycosylation variant of hCG produced by root cytotrophoblast cells and extravillous cytotrophoblast cells [ 6 , 7 ].
While hCG has monoantennary 8 sugar residues and biantennary 11 sugar residues N-linked oligosaccharides, and mostly trisaccharide O-linked oligosaccharides 3 sugar residues , hyperglycosylated hCG has mostly larger fucosylated triantennary 15 sugars N-linked oligosaccharides and double-size hexasaccharide O-linked oligosaccharides 6 sugar residues. As a result the molecular weight of hCG is 36,, while the molecular weight of hyperglycosylated hCG is 40, to 41,, dependent on extent of hyperglycosylation.
This exposes other receptor binding site on hyperglycosylated hCG. This still needs to be proven by needed research. As shown, hyperglycosylated hCG is the principal variant of hCG produced in early pregnancy. This is consistent with hyperglycosylated hCG having a function in promoting implantation in early pregnancy [ 8 , 9 , 87 ].
Research clearly shows that hyperglycosylated hCG acts on choriocarcinoma cells cancer of cytotrophoblast cells promoting invasion [ 9 , 10 ]. Hyperglycosylated hCG is the principal variant of hCG made by choriocarcinoma cells [ 9 , 10 ]. The role of hyperglycosylated hCG in choriocarcinoma invasion has been demonstrated now by 3 independent groups, each showing that this molecules promotes invasion by choriocarcinoma cells in Matrigel chambers [ 9 , 71 , 88 ].
Other studies examine growth of choriocarcinoma cells transplanted into nude mice in vivo [ 9 , 71 , 88 ]. These finding all suggest the use of blockage agent such as an antibody to hyperglycosylated hCG in the treatment of choriocarcinoma. Other research indicates that hyperglycosylated hCG, the cytotrophoblast cell invasion promoter in choriocarcinoma, specifically promotes the invasion in implantation of pregnancy, and the deep implantation of the villous placental structures that is driven by extravillous cytotrophoblast cells [ 6 , 8 , 87 ].
These studies used the B assay for hyperglycosylated hCG. Laboratory experiments show that antibody to hyperglycosylated hCG, antibody B, blocks growth of cytotrophoblast cell lines in vitro JEG-3 and Jar cell line. Hyperglycosylated hCG promotes growth of cytotrophoblast cells, at implantation and in choriocarcinoma [ 9 , 10 , 87 ]. As published [ 89 , 90 ], two third of pregnancy failures, biochemical pregnancies and miscarriages of pregnancy, are due to failure of blastocysts to implant appropriately.
The remaining one third of failures are due to hydatidiform mole or genetic abnormalities [ 89 , 90 ]. A total of 62 pregnancies were investigated. It is inferred that pregnancy failures are due to insufficient production of hyperglycosylated hCG leading to failure to implant appropriately. Similar finding showing that hyperglycosylated hCG is a marker of pregnancy failure have been reported by Kovalevskaya et al [ 91 ], also using the B specific assay.
Similarly, hypertense disorders of pregnancy or preeclampsia in pregnancy are due to failure to appropriately connect the implanting villous hemochorial placentation with appropriate uterine blood supply [ 92 , 93 ]. Studies indicate that this may also be due to a deficiency of hyperglycosylated hCG [ 94 ]. In conclusion, hyperglycosylated hCG is the invasive signal of cytotrophoblast invasion of pregnancy implantation and choriocarcinoma invasion. Ineffective invasion due to insufficient hyperglycosylated hCG occurs in failed pregnancies, biochemical pregnancies and miscarriages, and seemingly in hypertense disorders of pregnancy.
Studies by Acevedo et al. This data is considered rather controversial. New data, however, seemingly confirms these findings in cervical cancer cells [ 99 ]. We hypothesize that they both bind the same receptor and function through similar pathways. Publications in the nineteen sixties, seventies and eighties suggested bacteria, crabs, and other bazaar sources to explain detection of hCG in non-pregnant individuals, including cancer cases [ — ].
We now have a better understanding of the various not pregnant sources of hCG. Possibilities today include non-trophoblastic cancer, as described in the preceding section, quiescent gestational trophoblastic disease [ ], familial hCG syndrome [ ], and as shown in this chapter pituitary hCG. It is now been 30 years since hCG was first demonstrated to originate from the pituitary gland [ ]. Since then, almost 40 publications have confirmed this observation and described how very low level hCG production accompanies luteinizing hormone LH production at the time of the mid-menstrual cycle pre-ovulatory surge, a normal part of normal pituitary physiology [ — ].
In medical practice, a positive hCG test prior to menopause suggests pregnancy or gestational trophoblastic disease [ — ]. A positive hCG test in perimenopausal and menopause, can represent a predicament to physicians. When an hCG positive patient is referred to an oncologist, they may be considered as having gestational trophoblastic diseases or a non-gestational malignancy, and may be placed on chemotherapy or given hysterectomy with the hope that hCG will disappear.
The hCG level will not change in patients treated this way, since it is natural hormone, pituitary hCG. Pituitary hCG has an identical amino acid structure to pregnancy hCG. It is unique, however, in having a variable portion of sulfated oligosaccharides [ ]. The sulfated groups are attached to N-acetylgalactosamine residues, which replaces galactose and sialic acid residues in N- and O-linked oligosaccharides. As found pituitary hCG with sulfated oligosaccharides has a shorter circulating half life that pregnancy hCG [ ].
As shown by Odell and Griffin [ , ], using an ultra-sensitive radioimmunoassay LH sensitivity 0. Pituitary hCG was detected in women in pulses in the luteal and follicular phases of the menstrual cycle which paralleled LH levels [ , ].
Injections of Gonadotropin releasing hormone GnRH were shown to directly promote circulating pituitary hCG levels in men and women, just as they similarly promotes LH levels [ , ]. It is inferred that pituitary hCG supplements pituitary LH in men and women [ 13 , ]. The mean hCG level was 1.
This recent study very much confirms the findings of Odell and Griffin showing that pituitary hCG mirrors pituitary LH levels [ , ]. The mass of hCG stored in an individual human pituitary gland, 0.
Publications show that pituitary hCG has approximately half the biological activity in promoting progesterone production of placental hCG [ ]. It is important that the corpus luteum keeps producing progesterone because loss of progesterone leads to shedding of the womb lining menstruation , which would prevent an embryo from implanting.
Human chorionic gonadotrophin is the embryonic hormone that ensures the corpus luteum continues to produce progesterone throughout the first trimester of pregnancy. As well as maintaining progesterone production from the ovary, human chorionic gonadotrophin may also play a role in making sure the lining of the uterus endometrium is ready to receive the implanting embryo. Recent studies have indicated that human chorionic gonadotrophin may help to increase the blood supply to the uterus and be involved in re-shaping the lining of the uterus in preparation for the implanting embryo.
Human chorionic gonadotrophin is produced by the trophoblast cells which surround the developing embryo at approximately day five of pregnancy. The amount of human chorionic gonadotrophin in the bloodstream doubles every days as development of the embryo and placenta continue, and levels peak at around six weeks of pregnancy. Following this peak, levels of human chorionic gonadotrophin fall although they remain detectable throughout pregnancy.
Once the placenta is established, it becomes the main source of progesterone production around week 12 of pregnancy , and human chorionic gonadotrophin is no longer required to maintain ovarian function. However, human chorionic gonadotrophin may have additional beneficial effects in the latter stages of pregnancy; such roles are currently being investigated by researchers. If you have not already visited your doctor the 5th week of pregnancy is a good time to do so. Pregnancy, Birth and Baby is not responsible for the content and advertising on the external website you are now entering.
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Chaunie Brusie. HCG is a hormone almost ex clusively produced during pregnancy, and plays an important role in sustaining an embryo until the placenta is formed.
At-home pregnancy tests work by detecting hCG in the urine. HCG is produced in very minimal quantities in non-pregnant women and men and does not appear to play an appreciable role in body functions.
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