human chorionic gonadotropin human chorionic gonadotropin human chorionic gonadotropin (hcg) is a hormone for the maternal recognition of pregnancy produced by trophoblast cells that are surrounding a growing embryo (syncytiotrophoblast initially), which eventually forms the placenta after implantation. the presence of hcg is detected in some pregnancy tests (hcg pregnancy strip tests). some cancerous tumors produce this hormone; therefore, elevated levels measured when the patient is not pregnant may lead to a cancer diagnosis and, if high enough, paraneoplastic syndromes, however, it is not known whether this production is a contributing cause, or an effect of carcinogenesis. the pituitary analog of hcg, known as luteinizing hormone (lh), is produced in the pituitary gland of males and females of all ages. chorionic gonadotropin,alpha polypeptideidentifierssymbolcgaalt. symbolsfsha, gpha, gpha1, hcg, lha, tshancbi gene1081hgnc1885omim118850refseqnm_000735uniprotp01215other datalocuschr. 6 q14-q21search forstructuresswiss-modeldomainsinterpro chorionic gonadotropin,beta polypeptideidentifierssymbolcgbalt. symbolscgb3ncbi gene1082hgnc1886omim118860refseqnm_000737uniprotp01233other datalocuschr. 19 q13.3search forstructuresswiss-modeldomainsinterpro various endogenous forms of hcg exist. the measurement of these diverse forms is used in the diagnosis of pregnancy and a variety of disease states. preparations of hcg from various sources have also been used therapeutically, by both medicine and quackery. as of december 6, 2011, the united states food and drug administration has prohibited the sale of "homeopathic" and over-the-counter hcg diet products and declared them fraudulent and illegal. beta-hcg is initially secreted by the syncytiotrophoblast. structure human chorionic gonadotropin is a glycoprotein composed of 237 amino acids with a molecular mass of 36.7 kda, approximately 14.5kda αhcg and 22.2kda βhcg. it is heterodimeric, with an α (alpha) subunit identical to that of luteinizing hormone (lh), follicle-stimulating hormone (fsh), thyroid-stimulating hormone (tsh), and β (beta) subunit that is unique to hcg. the α (alpha) subunit is 92 amino acids long. the β-subunit of hcg gonadotropin (beta-hcg) contains 145 amino acids, encoded by six highly homologous genes that are arranged in tandem and inverted pairs on chromosome 19q13.3 - cgb (1, 2, 3, 5, 7, 8). it is known that cgb7 has a sequence slightly different from that of the others. the two subunits create a small hydrophobic core surrounded by a high surface area-to-volume ratio: 2.8 times that of a sphere. the vast majority of the outer amino acids are hydrophilic. beta-hcg is mostly similar to beta-lh, with the exception of a carboxy terminus peptide (beta-ctp) containing four glycosylated serine residues that is responsible for hcg's longer half-life. function human chorionic gonadotropin interacts with the lhcg receptor of the ovary and promotes the maintenance of the corpus luteum for the maternal recognition of pregnancy at the beginning of pregnancy. this allows the corpus luteum to secrete the hormone progesterone during the first trimester. progesterone enriches the uterus with a thick lining of blood vessels and capillaries so that it can sustain the growing fetus. it has been hypothesized that hcg may be a placental link for the development of local maternal immunotolerance. for example, hcg-treated endometrial cells induce an increase in t cell apoptosis (dissolution of t cells). these results suggest that hcg may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the trophoblast invasion, which is known to expedite fetal development in the endometrium. it has also been suggested that hcg levels are linked to the severity of morning sickness or hyperemesis gravidarum in pregnant women. because of its similarity to lh, hcg can also be used clinically to induce ovulation in the ovaries as well as testosterone production in the testes. as the most abundant biological source is in women who are presently pregnant, some organizations collect urine from pregnant women to extract hcg for use in fertility treatment. human chorionic gonadotropin also plays a role in cellular differentiation/proliferation and may activate apoptosis. production naturally, it is produced in the human placenta by the syncytiotrophoblast. like any other gonadotropins, it can be extracted from the urine of pregnant women or produced from cultures of genetically modified cells using recombinant dna technology. in pubergen, pregnyl, follutein, profasi, choragon and novarel, it is extracted from the urine of pregnant women. in ovidrel, it is produced with recombinant dna technology. hcg forms three major forms of hcg are produced by humans, with each having distinct physiological roles. these include regular hcg, hyperglycosylated hcg, and the free beta-subunit of hcg. degradation products of hcg have also been detected, including nicked hcg, hcg missing the c-terminal peptide from the beta-subunit, and free alpha-subunit, which has no known biological function. some hcg is also made by the pituitary gland with a pattern of glycosylation that differs from placental forms of hcg. regular hcg is the main form of hcg associated with the majority of pregnancy and in non-invasive molar pregnancies. this is produced in the trophoblast cells of the placental tissue. hyperglycosylated hcg is the main form of hcg during the implantation phase of pregnancy, with invasive molar pregnancies, and with choriocarcinoma. gonadotropin preparations of hcg can be produced for pharmaceutical use from animal or synthetic sources. testing blood or urine tests measure hcg. these can be pregnancy tests. hcg-positive can indicate an implanted blastocyst and mammalian embryogenesis or can be detected for a short time following childbirth or pregnancy loss. tests can be done to diagnose and monitor germ cell tumors and gestational trophoblastic diseases. concentrations are commonly reported in thousandth international units per milliliter (miu/ml). the international unit of hcg was originally established in 1938 and has been redefined in 1964 and in 1980. at the present time, 1 international unit is equal to approximately 2.35×10−12 moles, or about 6×10−8 grams. it is also possible to test for hcg to have an approximation of the gestational age. methodology most tests employ a monoclonal antibody, which is specific to the β-subunit of hcg (β-hcg). this procedure is employed to ensure that tests do not make false positives by confusing hcg with lh and fsh. (the latter two are always present at varying levels in the body, whereas the presence of hcg almost always indicates pregnancy.) many hcg immunoassays are based on the sandwich principle, which uses antibodies to hcg labeled with an enzyme or a conventional or luminescent dye. pregnancy urine dipstick tests are based on the lateral flow technique. the urine test may be a chromatographic immunoassay or any of several other test formats, home-, physician's office-, or laboratory-based. published detection thresholds range from 20 to 100 miu/ml, depending on the brand of test. early in pregnancy, more accurate results may be obtained by using the first urine of the morning (when urine is most concentrated). when the urine is dilute (specific gravity less than 1.015), the hcg concentration may not be representative of the blood concentration, and the test may be falsely negative. the serum test, using 2-4 ml of venous blood, is typically a chemiluminescent or fluorimetric immunoassay that can detect βhcg levels as low as 5 miu/ml and allows quantification of the βhcg concentration. reference levels in normal pregnancy the following is a list of serum hcg levels. (lmp is the last menstrual period dated from the first day of the last menstrual period.) the levels grow exponentially after conception and implantation. weeks since lmpmiu/ml 35 – 50 45 – 428 518 – 7,340 61,080 – 56,500 7 – 87,650 – 229,000 9 – 1225,700 – 288,000 13 – 1613,300 – 254,000 17 – 244,060 – 165,400 25 – 403,640 – 117,000 non-pregnant females<5.0 postmenopausal females<9.5 if a pregnant woman has serum hcg levels that are higher than expected, they may be experiencing a multiple pregnancy or an abnormal uterine growth. falling hcg levels may indicate the possibility of a miscarriage. hcg levels which are rising at a slower rate than expected may indicate an ectopic pregnancy. interpretation the ability to quantitate the βhcg level is useful in monitoring germ cell and trophoblastic tumors, follow-up care after miscarriage, and diagnosis of and follow-up care after treatment of ectopic pregnancy. the lack of a visible fetus on vaginal ultrasound after βhcg levels reach 1500 miu/ml is strongly indicative of an ectopic pregnancy. still, even an hcg over 2000 iu/l does not necessarily exclude the presence of a viable intrauterine pregnancy in such cases. as pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hcg between 6 and 12 days after ovulation. it must be taken into account, however, that total hcg levels may vary in a very wide range within the first 4 weeks of gestation, leading to false results during this period. a rise of 35% over 48 hours is proposed as the minimal rise consistent with a viable intrauterine pregnancy. gestational trophoblastic disease like hydatidiform moles ("molar pregnancy") or choriocarcinoma may produce high levels of βhcg (due to the presence of syncytiotrophoblasts - part of the villi that make up the placenta) despite the absence of an embryo. this, as well as several other conditions, can lead to elevated hcg readings in the absence of pregnancy. hcg levels are also a component of the triple test, a screening test for certain fetal chromosomal abnormalities/birth defects. a study of 32 normal pregnancies came to the result that a gestational sac of 1–3 mm was detected at a mean hcg level of 1150 iu/l (range 800–1500), a yolk sac was detected at a mean level of 6000 iu/l (range 4500–7500) and fetal heartbeat was visible at a mean hcg level of 10,000 iu/l (range 8650–12,200). uses tumor marker human chorionic gonadotropin can be used as a tumor marker, as its β subunit is secreted by some cancers including seminoma, choriocarcinoma, teratoma with elements of choriocarcinoma, other germ cell tumors, hydatidiform mole, and islet cell tumor. for this reason, a positive result in males can be a test for testicular cancer. the normal range for men is between 0-5 miu/ml. combined with alpha-fetoprotein, β-hcg is an excellent tumor marker for the monitoring of germ cell tumors. fertility human chorionic gonadotropinclinical datatrade namesnovarel, pregnylahfs/drugs.commonographatc codeg03ga08 (who) identifierscas number9002-61-3 ydrugbankdb00097 nchemspidernoneunii20ed16ghebcomptox dashboard (epa)dtxsid4036770 echa infocard100.029.679 chemical and physical dataformulac1105h1770n318o336s26molar mass25719.70 g·mol−1 ny (what is this?) human chorionic gonadotropin injection is extensively used for final maturation induction in lieu of luteinizing hormone. in the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of hcg. as ovulation will happen between 38 and 40 hours after a single hcg injection, procedures can be scheduled to take advantage of this time sequence, such as intrauterine insemination or sexual intercourse. also, patients that undergo ivf, in general, receive hcg to trigger the ovulation process, but have an oocyte retrieval performed at about 34 to 36 hours after injection, a few hours before the eggs actually would be released from the ovary. as hcg supports the corpus luteum, administration of hcg is used in certain circumstances to enhance the production of progesterone. in the male, hcg injections are used to stimulate the leydig cells to synthesize testosterone. the intratesticular testosterone is necessary for spermatogenesis from the sertoli cells. typical uses for hcg in men include hypogonadism and fertility treatment, including during testosterone replacement therapy to restore or maintain fertility and prevent testicular atrophy. several vaccines against human chorionic gonadotropin (hcg) for the prevention of pregnancy are currently in clinical trials. hcg pubergen, pregnyl warnings in the case of female patients who want to be treated with hcg pubergen, pregnyl: a) since infertile female patients who undergo medically assisted reproduction (especially those who need in vitro fertilization), are known to often be suffering from tubal abnormalities, after a treatment with this drug they might experience many more ectopic pregnancies. this is why early ultrasound confirmation at the beginning of a pregnancy (to see whether the pregnancy is intrauterine or not) is crucial. pregnancies that have occurred after a treatment with this drug have a higher risk of multiple pregnancy. female patients who have thrombosis, severe obesity, or thrombophilia should not be prescribed this medicine as they have a higher risk of arterial or venous thromboembolic events after or during a treatment with hcg pubergen, pregnyl. b)female patients who have been treated with this medicine are usually more prone to pregnancy losses. in the case of male patients: a prolonged treatment with hcg pubergen, pregnyl is known to regularly lead to increased production of androgen. therefore: patients who have overt or latent cardiac failure, hypertension, renal dysfunction, migraines, or