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Human chorionic gonadotropin

Human chorionic gonadotropin

Overview
Human chorionic gonadotropin or human chorionic gonadotrophin (hCG) is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 produced during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 that is made by the developing embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

 after conception and later by the syncytiotrophoblast
Syncytiotrophoblast
Syncytiotrophoblast is the epithelial covering of the placenta villous tree. It is a unique tissue in that it is a multi-nucleated, terminally differentiated syncytium, extending to 13m^2...

 (part of the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

).. Some tumors make this hormone; measured elevated levels when the patient is not pregnant can lead to a cancer diagnosis. However, it is not known whether this production is a contributing cause or an effect of tumorigenesis.
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Encyclopedia
Human chorionic gonadotropin or human chorionic gonadotrophin (hCG) is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 produced during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 that is made by the developing embryo
Embryo
An embryo is a multicellular diploid eukaryote in its earliest stage of development, from the time of first cell division until birth, hatching, or germination...

 after conception and later by the syncytiotrophoblast
Syncytiotrophoblast
Syncytiotrophoblast is the epithelial covering of the placenta villous tree. It is a unique tissue in that it is a multi-nucleated, terminally differentiated syncytium, extending to 13m^2...

 (part of the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...

).. Some tumors make this hormone; measured elevated levels when the patient is not pregnant can lead to a cancer diagnosis. However, it is not known whether this production is a contributing cause or an effect of tumorigenesis. The pituitary analog of hCG, known as luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

 (LH), is produced in the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

 of males and females of all ages. Since the mid-20th century, hCG has been promoted as a supplement to promote weight loss, though there has been no proof that it is effective or safe.

Structure


Human chorionic gonadotropin is a glycoprotein
Glycoprotein
Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 composed of 244 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

s with a molecular mass
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...

 of 36.7 kDa
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...

.

It is heterodimeric, with an α (alpha) subunit
Protein subunit
In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...

 identical to that of luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

 (LH), follicle-stimulating hormone
Follicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...

 (FSH), thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...

 (TSH), and β (beta) subunit that is unique to hCG.
  • The α (alpha)
    Chorionic gonadotropin alpha
    Glycoprotein hormones alpha chain is a protein that in humans is encoded by the CGA gene.-Further reading:...

     subunit
    Protein subunit
    In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles with other protein molecules to form a protein complex: a multimeric or oligomeric protein. Many naturally occurring proteins and enzymes are multimeric...

     is 92 amino acids long. The sequence of the alpha unit can be found on UniProtKB with ID: P01215[25-116].

  • The β-subunit of hCG gonadotropin contains 145 amino acids, encoded by six highly-homologous gene
    Gene
    A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

    s that are arranged in tandem and inverted pairs on chromosome 19q13.3 - CGB (1
    CGB1
    Choriogonadotropin subunit beta variant 1 is a protein that in humans is encoded by the CGB1 gene.-Further reading:...

    , 2
    CGB2 (gene)
    Choriogonadotropin subunit beta variant 2 is a protein that in humans is encoded by the CGB2 gene.-Further reading:...

    , 3, 5, 7
    CGB7
    Choriogonadotropin subunit beta is a protein that in humans is encoded by the CGB7 gene.-Further reading:...

    , 8). The sequence of the beta unit can be found on UniProtKB with ID: P01233[21-165].


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.

Function


Human chorionic gonadotropin interacts with the LHCG receptor and promotes the maintenance of the corpus luteum
Corpus luteum
The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...

 during the beginning of pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

, causing it to secrete the hormone progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

. Progesterone enriches the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...

 with a thick lining of blood vessel
Blood vessel
The blood vessels are the part of the circulatory system that transports blood throughout the body. There are three major types of blood vessels: the arteries, which carry the blood away from the heart; the capillaries, which enable the actual exchange of water and chemicals between the blood and...

s and capillaries
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...

 so that it can sustain the growing fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

. Due to its highly-negative charge, hCG may repel the immune cells of the mother, protecting the fetus during the first trimester. It has also 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
Morning sickness
Morning sickness, also called nausea gravidarum, nausea, vomiting of pregnancy , or pregnancy sickness is a condition that affects more than half of all pregnant women. Related to increased oestrogen levels, a similar form of nausea is also seen in some women who use hormonal contraception or...

 in pregnant women.

Because of its similarity to LH
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

, hCG can also be used clinically to induce ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...

 in the ovaries
Ovary
The ovary is an ovum-producing reproductive organ, often found in pairs as part of the vertebrate female reproductive system. Ovaries in anatomically female individuals are analogous to testes in anatomically male individuals, in that they are both gonads and endocrine glands.-Human anatomy:Ovaries...

 as well as testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 production in the testes. As the most abundant biological source is women who are presently pregnant, some organizations collect urine from pregnant women to extract hCG for use in fertility treatment
Assisted reproductive technology
Assisted reproductive technology is a general term referring to methods used to achieve pregnancy by artificial or partially artificial means. It is reproductive technology used primarily in infertility treatments. Some forms of ART are also used in fertile couples for genetic reasons...

.

Human chorionic gonadotropin also plays a role in cellular differentiation
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...

/proliferation and may activate apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...

.

Production


Like other gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...

s, hCG can be extracted from urine or by genetic modification. Pregnyl, Follutein, Profasi, Choragon and Novarel use the former method, derived from the urine of pregnant women. Ovidrel, on the other hand, is a product of recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...

. hCG is produced from the syncytiotrophoblast cell layer.

Testing


Levels of hCG may be measured in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....

 or urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

. Most commonly, this is done as a pregnancy test
Pregnancy test
A pregnancy test attempts to determine whether or not a woman is pregnant.These markers are found in urine and blood, and pregnancy tests require sampling one of these substances. The first of these markers to be discovered, human chorionic gonadotropin , was discovered in 1930 to be produced by...

, intended to indicate the presence or absence of an implanted embryo
Mammalian embryogenesis
Mammalian embryogenesis is the process of cell division and cellular differentiation during early prenatal development which leads to the development of a mammalian embryo.-Difference from human embryogenesis:...

. Testing for hCG may also be done when diagnosing or monitoring germ cell tumor
Germ cell tumor
A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...

s and gestational trophoblastic disease
Gestational trophoblastic disease
Gestational trophoblastic disease is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to grow out of control. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to...

.

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
Type I and type II errors
In statistical test theory the notion of statistical error is an integral part of hypothesis testing. The test requires an unambiguous statement of a null hypothesis, which usually corresponds to a default "state of nature", for example "this person is healthy", "this accused is not guilty" or...

 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.)
  • The urine test may be a chromatographic immunoassay
    Immunoassay
    An immunoassay is a biochemical test that measures the presence or concentration of a substance in solutions that frequently contain a complex mixture of substances. Analytes in biological liquids such as serum or urine are frequently assayed using immunoassay methods...

    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 hCG levels are highest). When the urine is dilute (specific gravity
    Specific gravity
    Specific gravity is the ratio of the density of a substance to the density of a reference substance. Apparent specific gravity is the ratio of the weight of a volume of the substance to the weight of an equal volume of the reference substance. The reference substance is nearly always water for...

     less than 1.015), the hCG concentration may not be representative of the blood concentration, and the test may be falsely negative.

  • The serum
    Blood plasma
    Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

     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. The ability to quantitate the βhCG level is useful in the monitoring germ cell
    Germ cell tumor
    A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...

     and trophoblastic tumors
    Gestational trophoblastic disease
    Gestational trophoblastic disease is a term used for a group of pregnancy-related tumours. These tumours are rare, and they appear when cells in the womb start to grow out of control. The cells that form gestational trophoblastic tumours are called trophoblasts and come from tissue that grows to...

    , followup care after miscarriage
    Miscarriage
    Miscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...

    , and in diagnosis of and follow-up care after treatment of ectopic pregnancy
    Ectopic pregnancy
    An ectopic pregnancy, or eccysis , is a complication of pregnancy in which the embryo implants outside the uterine cavity. With rare exceptions, ectopic pregnancies are not viable. Furthermore, they are dangerous for the parent, since internal haemorrhage is a life threatening complication...

    . The lack of a visible fetus on vaginal ultrasound
    Ultrasound
    Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...

     after the βhCG levels have reached 1500 mIU/ml is strongly indicative of an ectopic pregnancy.


As pregnancy tests, quantitative blood tests and the most sensitive urine tests usually detect hCG between 6 to 12 days after ovulation. However, it must be taken into account 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 of time.

Gestational trophoblastic disease like Hydatidiform mole
Hydatidiform mole
Molar pregnancy is an abnormal form of pregnancy, wherein a non-viable, fertilized egg implants in the uterus, and thereby converts normal pregnancy processes into pathological ones. It is characterized by the presence of a hydatidiform mole...

s ("molar pregnancy") or Choriocarcinoma may produce high levels of βhCG (due to the presence of syncytialtrophoblasts- 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
Triple test
The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities .The term "multiple-marker screening test" is sometimes used...

, a screening test for certain fetal chromosomal abnormalities/birth defects.

Reference levels


The following is a list of serum hCG levels. (LMP is the last menstrual period.) The levels grow exponentially after conception and implantation.
weeks since LMP mIU/mL
3 5 – 50
4 5 – 426
5 18 – 7,340
6 1,080 – 56,500
7 – 8 7,650 – 229,000
9 – 12 25,700 – 288,000
13 – 16 13,300 – 254,000
17 – 24 4,060 – 165,400
25 – 40 3,640 – 117,000
Non-pregnant females <5.0
Postmenopausal females <9.5

Tumor marker


Human chorionic gonadotropin can be used as a tumor marker
Tumor marker
A tumor marker is a substance found in the blood, urine, or body tissues that can be elevated in cancer, among other tissue types. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer...

, as its β subunit is secreted by some cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

s including seminoma, choriocarcinoma
Choriocarcinoma
Choriocarcinoma is a malignant, trophoblastic and aggressive cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs...

, germ cell tumor
Germ cell tumor
A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...

s, hydatidiform mole
Hydatidiform mole
Molar pregnancy is an abnormal form of pregnancy, wherein a non-viable, fertilized egg implants in the uterus, and thereby converts normal pregnancy processes into pathological ones. It is characterized by the presence of a hydatidiform mole...

 formation, teratoma
Teratoma
A teratoma is an encapsulated tumor with tissue or organ components resembling normal derivatives of all three germ layers. There are rare occasions when not all three germ layers are identifiable...

 with elements of choriocarcinoma
Choriocarcinoma
Choriocarcinoma is a malignant, trophoblastic and aggressive cancer, usually of the placenta. It is characterized by early hematogenous spread to the lungs...

, and islet cell tumor. For this reason a positive result in males can be a test for testicular cancer
Testicular cancer
Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system.In the United States, between 7,500 and 8,000 diagnoses of testicular cancer are made each year. In the UK, approximately 2,000 men are diagnosed each year. Over his lifetime, a man's risk of...

. The normal range for men is between 0-5 mIU/mL. Combined with alpha-fetoprotein
Alpha-fetoprotein
Alpha-fetoprotein is a protein that in humans is encoded by the AFP gene....

, β-HCG is an excellent tumor marker for the monitoring of germ cell tumor
Germ cell tumor
A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...

s.

Fertility



Human chorionic gonadotropin is extensively used parenteral
Parenteral
Parenteral is a route of administration that involves piercing the skin or mucous membrane. Parenteral nutrition refers to providing nutrition via the veins.-Etymology:...

ly as an ovulation inducer
Ovulation induction
Ovulation induction is the stimulation of ovulation by medication. It is usually used in the sense of stimulation of the development of ovarian follicles to reverse anovulation or oligoovulation, but can also be used in the sense of triggering oocyte release from relatively mature ovarian follicles...

 in lieu of luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of hCG. As ovulation
Ovulation
Ovulation is the process in a female's menstrual cycle by which a mature ovarian follicle ruptures and discharges an ovum . Ovulation also occurs in the estrous cycle of other female mammals, which differs in many fundamental ways from the menstrual cycle...

 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 a oocyte retrieval performed at about 34 to 36 hours after injection by, a few hours before the eggs actually would be released from the ovary.

As hCG supports the corpus luteum
Corpus luteum
The corpus luteum is a temporary endocrine structure in mammals, involved in production of relatively high levels of progesterone and moderate levels of estradiol and inhibin A...

, administration of hCG is used in certain circumstances to enhance the production of progesterone
Progesterone
Progesterone also known as P4 is a C-21 steroid hormone involved in the female menstrual cycle, pregnancy and embryogenesis of humans and other species...

.

In the male, hCG injections are used to stimulate the leydig cell
Leydig cell
Leydig cells, also known as interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle. They produce testosterone in the presence of luteinizing hormone...

s to synthesize testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

. The intratesticular testosterone is necessary for spermatogenesis
Spermatogenesis
Spermatogenesis is the process by which male primary germ cells undergo division, and produce a number of cells termed spermatogonia, from which the primary spermatocytes are derived. Each primary spermatocyte divides into two secondary spermatocytes, and each secondary spermatocyte into two...

 from the sertoli cells. Typical uses for hCG in men include hypogonadism
Hypogonadism
Hypogonadism is a medical term for decreased functional activity of the gonads. Low testosterone is caused by a decline or deficiency in gonadal production of testosterone in males...

 and fertility treatment.

During first few months of pregnancy, the transmission of HIV-1 from woman to fetus is extremely rare. It has been suggested that this is due to the high concentration of hCG, and that the beta-subunit of this protein is active against HIV-1.

Weight loss


A controversial usage of hCG is as an adjunct to the British endocrinologist Albert T. W. Simeons
Albert T. W. Simeons
Dr. Albert T. W. Simeons, , english endocrinologist, schooled in Germany. During short stay in Africa he wanted to find a cure for Tropical Diseases. Then he went to India in 1930. He was awarded with the Red Cross Order of Merit for his discoveries in new methods that could lead to a cure for...

' ultra-low-calorie weight-loss diet (less than 500 calories). Simeons, while studying pregnant women in India on a calorie-deficient diet, and “fat boys” with pituitary problems (Frölich's syndrome) treated with low-dose hCG, claimed that both lost fat rather than lean (muscle) tissue. He reasoned that hCG must be programming the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 to do this in the former cases in order to protect the developing fetus by promoting mobilization and consumption of abnormal, excessive adipose deposits. Simeons later published a book entitled Pounds and Inches, designed to combat obesity. Simeons, practicing at Salvator Mundi International Hospital in Rome, Italy, recommended low-dose daily hCG injections (125 IU) in combination with a customized ultra-low-calorie (500 cal/day, high-protein, low-carbohydrate/fat) diet loss of adipose tissue without loss of lean tissue. After Simeons’ death, the diet started to spread to specialized centers and via popularization by individuals, such as the controversial author Kevin Trudeau
Kevin Trudeau
Kevin Mark Trudeau is an American author, radio personality, and infomercial salesman best known for promoting alternative medicine. A number of his television infomercials and several of his books, including Natural Cures "They" Don't Want You to Know About, allege that both the U.S...

, famous for promotion of alternative therapies and treatments.

The controversy proceeds from warnings by the Journal of the American Medical Association
Journal of the American Medical Association
The Journal of the American Medical Association is a weekly, peer-reviewed, medical journal, published by the American Medical Association. Beginning in July 2011, the editor in chief will be Howard C. Bauchner, vice chairman of pediatrics at Boston University’s School of Medicine, replacing ...

 and the American Journal of Clinical Nutrition that hCG is neither safe nor effective as a weight-loss aid. However, recent studies in the Journal of Clinical Endocrinology and Metabolism
Journal of Clinical Endocrinology and Metabolism
The Journal of Clinical Endocrinology and Metabolism is a peer-reviewed medical journal in the field of endocrinology and metabolism. The current editor-in-chief is Leonard Wartofsky.-External links:...

 show hCG can have an effect on the lean body mass of older men with androgen deficiency.

A meta analysis found that studies supporting hCG for weight loss were of poor methodological quality and concluded that "there is no scientific evidence that HCG is effective in the treatment of obesity; it does not bring about weight-loss or fat-redistribution, nor does it reduce hunger or induce a feeling of well-being".

Homeopathic hCG for weight control


Controversy about, and shortages of, injected hCG for weight loss have led to substantial Internet promotion of "homeopathic
Homeopathy
Homeopathy is a form of alternative medicine in which practitioners claim to treat patients using highly diluted preparations that are believed to cause healthy people to exhibit symptoms that are similar to those exhibited by the patient...

 hCG" for weight control. The ingredients in these products are often obscure, but if prepared from true hCG via homeopathic dilution, they contain either no hCG at all or only trace amounts.

The United States Food and Drug Administration
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...

 has stated that this drug is fraudulent and ineffective for weight loss. It is also not protected as a homeopathic drug and has been deemed an illegal substance.

According to the studies noted above, the weight loss indicated by individuals on an "hCG diet" can be attributed entirely to the fact that such diets prescribe a consumption rate of 500-550 calorie per day, or approximately one quarter of what is commonly accepted as the daily recommended value for a male adult of average build and activity. Further, double-blind studies note no decrease in appetite by those taking hCG versus individuals on placebos and have offered no evidence that individuals taking hCG are more likely to lose fat than lean tissue. Long-term results caution that unlike individuals participating in a diet of, for example, 1100 calories per day those on a 500 calorie per day diet are unlikely to develop more appropriate eating habits and will gain weight more quickly after the diet has completed.

HCG Pregnyl Warnings


In the case of female patients who want to be treated with HCG Pregnyl:
a) Since infertile female patients who undergo medically assisted reproduction (especially those who need in vitro fertilization
In vitro fertilisation
In vitro fertilisation is a process by which egg cells are fertilised by sperm outside the body: in vitro. IVF is a major treatment in infertility when other methods of assisted reproductive technology have failed...

), 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 who have occurred after a treatment with this medicine are submitted to a higher risk of multiplets. - 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 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 Pregnyl is known to regularly lead to increased production of androgen. Therefore: Patients who are suffering from overt or latent cardiac failure, hypertension, renal dysfunction, migraine or Epilepsy might not be allowed to start using this medicine or might have to be prescribed a lower dose of HCG Pregnyl. Also this medicine should be used with extreme cautious in the case of prepubertal teenagers in order to reduce the risk of experiencing precocious sexual development or premature epiphyseal closure. This type of patients’ skeletal maturation should be closely and regularly monitored.

Both male and female patients who have the following medical conditions must not start a treatment with HCG Pregnyl:1)Hypersensitivity to this medicine or to any of its main ingredients. 2)Known or possible androgen-dependent tumors for example male breast carcinoma or prostatic carcinoma.

Anabolic steroid adjunct


In the world of performance-enhancing drugs, hCG is increasingly used in combination with various anabolic androgenic steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...

 (AAS) cycles. As a result, hCG is included in some sports' illegal drug lists.

When exogenous AAS are put into the male body, natural negative-feedback loops cause the body to shut down its own production of testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...

 via shutdown of the hypothalamic-pituitary-gonadal axis (HPGA
Hypothalamic-pituitary-gonadal axis
The hypothalamic–pituitary–gonadal axis refers to the effects of the hypothalamus, pituitary gland, and gonads as if these individual endocrine glands were a single entity as a whole...

). This causes testicular atrophy, among other things. hCG is commonly used during and after steroid cycles to maintain and restore testicular size as well as normal testosterone production.

High levels of AASs, that mimic the body's natural testosterone, trigger the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 to shut down its production of gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...

 (GnRH) from the hypothalamus. Without GnRH, the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...

 stops releasing luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...

 (LH). LH normally travels from the pituitary via the blood stream to the testes
Testicle
The testicle is the male gonad in animals. Like the ovaries to which they are homologous, testes are components of both the reproductive system and the endocrine system...

, where it triggers the production and release of testosterone. Without LH, the testes shut down their production of testosterone. In males, hCG helps restore and maintain testosterone production in the testes by mimicking LH and triggering the production and release of testosterone.

If hCG is used for too long and in too high a dose, the resulting rise in natural testosterone will eventually inhibit its own production via negative feedback on the hypothalamus and pituitary gland.

Professional athletes who have tested positive for hCG have been temporarily banned from their sport, including a 50-game ban from MLB for Manny Ramirez
Manny Ramírez
Manuel "Manny" Arístides Ramírez Onelcida is a retired Dominican-American professional baseball outfielder. He was recognized for great batting skill and power, a nine-time Silver Slugger and one of 25 players to hit 500 career home runs. Ramirez's 21 grand slams are third all-time, and his 28...

 in 2009 and a 4-game ban from the NFL for Brian Cushing
Brian Cushing
-Houston Texans:Cushing was drafted with the 15th overall pick in the 2009 NFL Draft by the Houston Texans.He scored his first career points on October 4, 2009 when he recorded a safety against the Oakland Raiders. The safety was the first recorded by a Texan since the 2002 season.Cushing was...

 for a positive urine test for hCG.

See also

  • Equine chorionic gonadotropin
    Equine chorionic gonadotropin
    Equine chorionic gonadotropin is a gonadotropic hormone produced in the chorion of pregnant mares. Most commonly called pregnant mare's serum gonadotropin in the past, the hormone is commonly used in concert with progestogen to induce ovulation in livestock prior to artificial...

  • Human placental lactogen
    Human placental lactogen
    Human placental lactogen , also called human chorionic somatomammotropin, is a polypeptide placental hormone. Its structure and function is similar to that of human growth hormone. It modifies the metabolic state of the mother during pregnancy to facilitate the energy supply of the fetus. HPL has...

  • Triple test
    Triple test
    The triple test, also called triple screen, the Kettering test or the Bart's test, is an investigation performed during pregnancy in the second trimester to classify a patient as either high-risk or low-risk for chromosomal abnormalities .The term "multiple-marker screening test" is sometimes used...

    - a screening test in pregnancy

External links