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J Clin Endocrinol Metab 86 , — Google Scholar. Clin Chem 41 , — Fertil Steril 74 , — 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 [ ]. As such, it is fold more potent than pituitary LH [ 15 ]. This makes pituitary hCG a significant pituitary hormone. As yet, it is unknown whether there is a specific function for pituitary hCG during the menstrual cycle.
Pituitary hCG could have functions separate from those of LH. But even if pituitary hCG has no specific function, there is a natural explanation for its production. LH has multiple functions during the LH peak and ovulation period. We assume that LH and hCG act on the same receptor on granulosa and theca cells. LH causes the follicle to form a stigma or protrusion [ ], and then promotes collagenase production to degrade and penetrate the stigma [ , ].
The penetration of the stigma causes bursting of the follicle ovulation to occur. LH then acts to differentiate the burst or ovulated follicle into a corpus luteum [ , ].
It is not clear whether hCG just incidentally assists LH in each of these steps or has specific functions of its own in one or more of these steps. Considering these critical biological functions there is a major paradox that exists. In serum, in the 4 th week of gestation weeks following start of menstrual period , individual total hCG values vary by fold, between 0.
Hyperglycosylated hCG values vary even wider during this week of pregnancy, fold. In the 5 th week of gestation total hCG values vary by fold, between 1. Hyperglycosylated hCG values vary once again slightly wider, fold. We ask how and why does this extremely wide variation exist with such important molecules between different pregnancies, and how with such extreme variation in signal, can all these pregnancies go to term and produce similar size babies?
This is the subject of two articles. The first article addresses the cause of the wide variation [ ], and the second article address the affect of the wide variation, or how the receptors cope with this situation [Cole LA, paper submitted to J Clin Endocrinol Metab ]. As published [ ], pregnancy data in normally anchored to the start of the last menstrual period.
Implantation of term outcome pregnancy biochemical pregnancies and miscarried pregnancies excluded or the start of gestation occured, however, anywhere from day 16 to day 32 from this anchoring point in 82 woman with menstrual cycle of average length of In a 28 day cycle this can be considered as anywhere from 12 days prior to missing a menstrual period to 2 days after the time of missing a menstrual period.
The day of implantation is 3 to 16 days after the LH peak. The day of implantation is the day of starting viable pregnancy. Dating this important date to the time of the start of the last menses weeks of gestation is a source of great variability [ , ]. If pregnancies were dated, however, to the day of implantation difficult to measure and difficult as an anchor date , variation is dropped significantly [ ]. If the same pregnancies were dated to 7 days after the time of implantation, hCG ranges from just 3.
Clearly dating pregnancies to time of implantation is preferable to dating to start of last menstrual period, but is difficult. Difficult in that it requires daily hCG measurements while attempting to achieve pregnancy to determine time of implantation.
Clearly dating of pregnancies is a cause of variation. Examining pregnancies from implantation to term, only one other cause could be found for individual variations in hCG.
That is hCG daily increase rate in the first 4 weeks following implantation. The increase rate per day was averaged over the 28 days. The increase rate per day ranged from 1. If this is considered over 7 days then it is equivalent to 1. Individual hCG daily amplification rate is also a major cause of variation.
It is a fact that pregnancy to pregnancy hCG levels vary greatly. How does the human body deal with these wide variations in hCG concentrations? How does each woman end up with a normal term delivery?
Most hCG and hyperglycosylated hCG-related parameters, like promotion of uterine vascular angiogenesis, promotion of implantation, differentiation of cytotrophoblast cells, growth and differentiation of fetal organs, are not readily measurable in normal term pregnancies. One hCG-related biological activity was, however, measurable, promotion of progesterone production by corpus luteal cells at weeks of gestation.
Serum progesterone was measured during the 4 th week of gestation, in those providing serum samples. During the 4 th week of pregnancy serum hCG ranged widely from 0. Serum progesterone during this same period, in these same women, did no vary widely, 6. Interestingly, in the case with extremely low serum hCG concentration, 0. The hCG levels stretched fold from 0. Under the spare receptor concept, when only a tiny proportion of receptors is activated in a cell it may yield a similar cellular response to all receptors on the cell being activated [ - ].
This is the best explanation of these findings. Similarly, in cases with extremely high serum hCG concentration lower than normal progesterone was observed. This is seemingly due to receptor down-regulation in the presence of high concentrations of hCG [ - ]. As demonstrated, high concentrations of hCG decrease the number of receptor on cells by degrading the receptor transcript in cells reducing their half-life [ ]. Just at the spare receptor mechanism deals with low hCG concentrations at the receptor level, the down-regulation mechanism deals with high hCG concentrations at the receptor level.
The end result is that the hCG and hyperglycosylated hCG variation paradox may be a simple case of "nature takes care of it. Following upregulation of cAMP, activation of phosphokinase A then occurs, resulting in phosphorylation and activation of the cAMP responsive element [ ].
Activation of protein kinase activates the mitogen protein kinase pathways and a Janus-kinase signaling pathway [ ]. Promotion of progesterone production in corpus luteal cells involves the synthesis of cholesterol side-chain cleavage enzyme. Fetal tissue growth involves protein synthesis. This activates exo- and endonuclease and leads to the destruction of receptor mRNA. This mechanism limits receptor expression, effectively down-regulating the receptor [ ].
Moreover, recent data suggest that in the case of hCG signaling at implantation and production of natural killer cells binding with a mannose receptor may be the activation mechanism [ , ].
While they may all be effective in different cells, they all have to be carefully considered as parts of the principal receptor mechanism. National Center for Biotechnology Information , U. Journal List Reprod Biol Endocrinol v. Reprod Biol Endocrinol. Published online Aug Laurence A Cole 1. Author information Article notes Copyright and License information Disclaimer.
Corresponding author. Laurence A Cole: moc. Received Jun 14; Accepted Aug This article has been cited by other articles in PMC. Abstract Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions.
Results and discussion hCG has numerous functions. Introduction It is difficult to say who specifically was the discoverer of the hormone we call hCG.
Table 1 The biological functions of the isoforms of hCG. Promotion of corpus luteal progesterone production [ 1 - 4 , 17 - 23 ] 2. Angiogenesis of uterine vasculature [ 24 - 30 ] 3. Cytotrophoblast differentiation [ 31 ] 4. Immuno-suppression and blockage of phagocytosis of invading trophoblast cells [ 32 - 38 ] 5. Growth of uterus in line with fetal growth [ 39 , 40 ] 6. Quiescence of uterine muscle contraction [ 39 , 41 - 43 ] 7. Promotion of growth and differentiation of fetal organs [ 44 - 49 ] 8.
Umbilical cord growth and development [ 51 - 53 ] 9. The human chorionic gonadotropin hCG test is done to measure the amount of the hormone hCG in blood or urine to see if a woman is pregnant. HCG may also be measured to see if cancer of the ovaries or testicles is present. These numbers are just a guide. The range for "normal" varies from lab to lab. Your lab may have a different range. Your lab report should show what range your lab uses for "normal. So a number that is outside the normal range here may still be normal for you.
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Updated visitor guidelines. Top of the page. HCG to detect pregnancy An egg is normally fertilized by a sperm cell in a fallopian tube.
HCG blood tests The level of hCG in the blood is often used as part of a screening for birth defects in a maternal serum triple or quadruple screening test. Health Tools Health Tools help you make wise health decisions or take action to improve your health. Decision Points focus on key medical care decisions that are important to many health problems. Find an ectopic pregnancy. Find and check the treatment of a molar pregnancy. See if there is a greater chance of birth defects such as Down syndrome.
The test is done with other screening tests. Find and check on the treatment of a cancer that develops from an egg or sperm germ cell cancer , such as cancer of the ovaries or testicles. In such cases, a test for alpha-fetoprotein may be done along with a test for hCG. How To Prepare If a blood sample is collected, you do not need to do anything before you have this test.
Blood sample collection The health professional drawing blood will: Wrap an elastic band around your upper arm to stop the flow of blood. This makes the veins below the band larger so it is easier to put a needle into the vein.
Clean the needle site with alcohol. Put the needle into the vein. If the needle is not placed correctly or if the vein collapses, more than one needle stick may be needed. Attach a tube to the needle to fill it with blood. Remove the band from your arm when enough blood is collected.
Put a gauze pad or cotton ball over the needle site as the needle is removed. Put pressure on the site and then put on a bandage. Urine collection If possible, collect a sample from the first urine of the day. Place the collection container into the stream of urine. Low levels of human chorionic gonadotrophin can indicate a failing pregnancy.
Reduced levels of human chorionic gonadotrophin are often observed in ectopic pregnancies where the embryo implants outside of the uterus or in miscarriages.
About Contact Events News. Search Search. You and Your Hormones. Students Teachers Patients Browse. Human body. Home Hormones Human chorionic gonadotrophin. Human chorionic gonadotrophin Human chorionic gonadotrophin is a reproductive hormone that is essential for establishing and maintaining early pregnancy.
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