choriogonadotropin Receptor
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Human chorionic gonadotropin (hCG) is a
hormone A hormone (from the Ancient Greek, Greek participle , "setting in motion") is a class of cell signaling, signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physio ...
for the maternal recognition of pregnancy produced by
trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...
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 test A pregnancy test is used to determine whether a person is Pregnancy, pregnant or not. The two primary methods are testing for the pregnancy hormone (human chorionic gonadotropin (hCG)) in blood or urine using a pregnancy test kit, and scanning ...
s (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 syndrome A paraneoplastic syndrome is a syndrome (a set of signs and symptoms) that is the consequence of a tumor in the body (usually a cancerous one). It is specifically due to the production of chemical signaling molecules (such as hormones or cytokin ...
s, however, it is unknown whether this production is a contributing cause or an effect of
carcinogenesis Carcinogenesis, also called oncogenesis or tumorigenesis, is the formation of a cancer, whereby normal cell (biology), cells are malignant transformation, transformed into cancer cells. The process is characterized by changes at the cellular, G ...
. The pituitary analog of hCG, known as
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
(LH), is produced in the
pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
of males and females of all ages. Beta-hCG is initially secreted by the
syncytiotrophoblast The syncytiotrophoblast (from the Greek 'syn'- "together"; 'cytio'- "of cells"; 'tropho'- "nutrition"; 'blast'- "bud") is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish ...
.


Structure

Human chorionic gonadotropin is a
glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known a ...
composed of 237
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s with a
molecular mass The molecular mass () is the mass of a given molecule, often expressed in units of daltons (Da). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The derived quan ...
of 36.7
kDa The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...
, approximately 14.5kDa αhCG and 22.2kDa βhCG. It is
heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
ic, with an α (alpha) subunit identical to that of
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
(LH),
follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...
(FSH), thyroid-stimulating hormone (TSH), and a 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
gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
s that are arranged in tandem and inverted pairs on
chromosome 19 Chromosome 19 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 19 spans more than 61.7 million base pairs, the building material of DNA. It is considered the most Gene density, gene-ri ...
q13.3 - ''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 In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
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 A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...
.; 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 The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
for the maternal recognition of pregnancy at the beginning of
pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...
. This allows the corpus luteum to
secrete Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...
the hormone
progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
during the first trimester. Progesterone enriches the
uterus The uterus (from Latin ''uterus'', : uteri or uteruses) or womb () is the hollow organ, organ in the reproductive system of most female mammals, including humans, that accommodates the embryonic development, embryonic and prenatal development, f ...
with a thick
lining Lining may refer to: * Lining (sewing), the process of inserting an inner layer of fabric, fur, or other material * Lining of paintings, the process of restoration paintings by attaching a new canvas to the back of the existing one * Brake lin ...
of
blood vessel Blood vessels are the tubular structures of a circulatory system that transport blood throughout many Animal, animals’ bodies. Blood vessels transport blood cells, nutrients, and oxygen to most of the Tissue (biology), tissues of a Body (bi ...
s and
capillaries A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the in ...
so that it can sustain the growing
fetus A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic development, embryonic stage, the fetal stage of development takes place. Pren ...
. 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 Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
(dissolution of
T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...
s). These results suggest that hCG may be a link in the development of peritrophoblastic immune tolerance, and may facilitate the
trophoblast The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...
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, also called nausea and vomiting of pregnancy (NVP), is a symptom of pregnancy. Despite the name, nausea or vomiting can occur at any time during the day. Typically the symptoms occur between the 4th and 16th weeks of pregnan ...
or
hyperemesis gravidarum Hyperemesis gravidarum (HG) is a pregnancy complication that is characterized by severe nausea, vomiting, weight loss, and possibly dehydration. Feeling faint may also occur. It is considered a more severe form of morning sickness. Symptoms ...
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 The syncytiotrophoblast (from the Greek 'syn'- "together"; 'cytio'- "of cells"; 'tropho'- "nutrition"; 'blast'- "bud") is the epithelial covering of the highly vascular embryonic placental villi, which invades the wall of the uterus to establish ...
. 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 Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
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 Recombinant DNA (rDNA) molecules are DNA molecules formed by laboratory methods of genetic recombination (such as molecular cloning) that bring together genetic material from multiple sources, creating sequences that would not otherwise be fo ...
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 The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
with a pattern of
glycosylation Glycosylation is the reaction in which a carbohydrate (or ' glycan'), i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule (a glycosyl acceptor) in order to form a glycoconjugate. In biology (but not ...
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 The trophoblast (from Greek language, Greek : to feed; and : germinator) is the outer layer of cells of the blastocyst. Trophoblasts are present four days after Human fertilization, fertilization in humans. They provide nutrients to the embryo an ...
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 Choriocarcinoma is a trophoblastic cancer usually located on the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also cla ...
.
Gonadotropin preparations Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication for ovarian hyperstimulation and ovulation induction. For example, the so-called menotropins consist ...
of hCG can be produced for pharmaceutical use from
animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...
or
synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...
sources.


Testing

Blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...
or
urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...
tests measure hCG. These can be
pregnancy test A pregnancy test is used to determine whether a person is Pregnancy, pregnant or not. The two primary methods are testing for the pregnancy hormone (human chorionic gonadotropin (hCG)) in blood or urine using a pregnancy test kit, and scanning ...
s. hCG-positive can indicate an implanted
blastocyst The blastocyst is a structure formed in the early embryonic development of mammals. It possesses an inner cell mass (ICM) also known as the ''embryoblast'' which subsequently forms the embryo, and an outer layer of trophoblast cells called the ...
and
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 embryogenesis of lower chordates Due to the fact that p ...
or can be detected for a short time following childbirth or pregnancy loss. Tests can be done to diagnose and monitor
germ cell tumor A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells. Germ-cell tumors can be cancerous or benign. Germ cell tumors typically originate from the gonads (ovary and testis), but can arise in other areas of the body. Extragon ...
s 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 A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test res ...
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 A urine test is any medical test performed on a urine specimen. The analysis of urine is a valuable diagnostic tool because its composition reflects the functioning of many body systems, particularly the kidneys and urinary system, and specimens ...
may be a ''chromatographic
immunoassay An immunoassay (IA) is a biochemical test that measures the presence or concentration of a macromolecule or a small molecule in a solution through the use of an antibody (usually) or an antigen (sometimes). The molecule detected by the 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 Relative density, also called specific gravity, is a dimensionless quantity defined as the ratio of the density (mass of a unit volume) of a substance to the density of a given reference material. Specific gravity for solids and liquids is nea ...
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 hCG levels grow exponentially after conception and implantation. hCG levels typically peak around weeks 8-11 of pregnancy and are generally higher in the first trimester compared to the second trimester. The following is a list of serum hCG levels: ''LMP'' is the
last menstrual period Menstruation (also known as a period, among other colloquial terms) is the regular discharge of blood and mucosal tissue from the inner lining of the uterus through the vagina. The menstrual cycle is characterized by the rise and fall of hor ...
dated from the first day of the last menstrual period If a pregnant woman has serum hCG levels that are higher than expected, they may be experiencing a
multiple pregnancy A multiple birth is the culmination of a multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such births ...
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 Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these sympto ...
.


Interpretation

The ability to quantitate the βhCG level is useful in monitoring
germ cell A germ cell is any cell that gives rise to the gametes of an organism that reproduces sexually. In many animals, the germ cells originate in the primitive streak and migrate via the gut of an embryo to the developing gonads. There, they unde ...
and trophoblastic tumors, follow-up care after
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion, is an end to pregnancy resulting in the loss and expulsion of an embryo or fetus from the womb before it can fetal viability, survive independently. Miscarriage before 6 weeks ...
, and diagnosis of and follow-up care after treatment of
ectopic pregnancy Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these sympto ...
. The lack of a visible fetus on vaginal
ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...
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.


Associations with pathologies

Gestational trophoblastic disease like
hydatidiform mole A molar pregnancy, also known as a hydatidiform mole, is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus. It falls under the category of gestational trophoblastic diseases. During a molar pregnancy, the ...
s ("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, and 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 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 (and n ...
, a screening test for certain fetal chromosomal abnormalities/birth defects. High hCG levels in the maternal serum could suggest Down syndrome, potentially due to continued hCG production by the placenta beyond the first trimester. A study of 32 normal pregnancies came to the result that a
gestational sac The gestational sac is the large cavity of fluid surrounding the embryo. During early embryogenesis, it consists of the extraembryonic coelom, also called the chorionic cavity. The gestational sac is normally contained within the uterus. It is the ...
of 1–3 mm was detected at a mean hCG level of 1150 IU/L (range 800–1500), a
yolk sac The yolk sac is a membranous wikt:sac, sac attached to an embryo, formed by cells of the hypoblast layer of the bilaminar embryonic disc. This is alternatively called the umbilical vesicle by the Terminologia Embryologica (TE), though ''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 A tumor marker is a biomarker that can be used to indicate the presence of cancer or the behavior of cancers (measure progression or response to therapy). They can be found in bodily fluids or tissue. Markers can help with assessing prognosis, s ...
, as its β subunit is secreted by some
cancer Cancer is a group of diseases involving Cell growth#Disorders, abnormal cell growth with the potential to Invasion (cancer), invade or Metastasis, spread to other parts of the body. These contrast with benign tumors, which do not spread. Po ...
s including
seminoma A seminoma is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations. It is a Malignancy, malignant neoplasm and is one of the most treatable and curable cancers, with a survival rate above 95% if di ...
,
choriocarcinoma Choriocarcinoma is a trophoblastic cancer usually located on the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also cla ...
,
teratoma A teratoma is a neoplasia, tumor made up of several types of biological tissue, tissue, such as hair, muscle, Human tooth, teeth, or bone. Teratomata typically form in the tailbone (where it is known as a sacrococcygeal teratoma), ovary, or test ...
with elements of
choriocarcinoma Choriocarcinoma is a trophoblastic cancer usually located on the placenta. It is characterized by early hematogenous spread to the lungs. It belongs to the malignant end of the spectrum in gestational trophoblastic disease (GTD). It is also cla ...
, other
germ cell tumor A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells. Germ-cell tumors can be cancerous or benign. Germ cell tumors typically originate from the gonads (ovary and testis), but can arise in other areas of the body. Extragon ...
s,
hydatidiform mole A molar pregnancy, also known as a hydatidiform mole, is an abnormal form of pregnancy in which a non-viable fertilized egg implants in the uterus. It falls under the category of gestational trophoblastic diseases. During a molar pregnancy, the ...
, and islet cell tumor. For this reason, a positive result in males can be a test for
testicular cancer Testicular cancer is cancer that develops in the testicles, a part of the male reproductive system. Symptoms may include a lump in the testicle or swelling or pain in the scrotum. Treatment may result in infertility. Risk factors include an c ...
. The normal range for men is between 0-5 mIU/mL. Combined with
alpha-fetoprotein Alpha-fetoprotein (AFP, α-fetoprotein; also sometimes called alpha-1-fetoprotein, alpha-fetoglobulin, or alpha fetal protein) is a protein that in humans is encoded by the ''AFP'' gene. The ''AFP'' gene is located on the ''q'' arm of chromosome ...
, β-HCG is an excellent tumor marker for the monitoring of
germ cell tumor A germ cell tumor (GCT) is a neoplasm derived from primordial germ cells. Germ-cell tumors can be cancerous or benign. Germ cell tumors typically originate from the gonads (ovary and testis), but can arise in other areas of the body. Extragon ...
s.


Fertility

Human chorionic gonadotropin injection is extensively used for final maturation induction in lieu of
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
. In the presence of one or more mature ovarian follicles, ovulation can be triggered by the administration of HCG. As
ovulation Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...
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 Artificial insemination is the deliberate introduction of sperm into a female's cervix or uterine cavity for the purpose of achieving a pregnancy through in vivo fertilization by means other than sexual intercourse. It is a fertility treatment ...
or sexual intercourse. Also, patients that undergo IVF, in general, receive HCG to trigger the ovulation process, but have an
oocyte retrieval Transvaginal oocyte retrieval (TVOR), also referred to as oocyte retrieval (OCR), is a technique used in in vitro fertilization (IVF) in order to remove oocytes from an ovary, enabling fertilization outside the body. Transvaginal 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 The corpus luteum (Latin for "yellow body"; : corpora lutea) is a temporary endocrine structure in female ovaries involved in the production of relatively high levels of progesterone, and moderate levels of estradiol, and inhibin A. It is the ...
, administration of hCG is used in certain circumstances to enhance the production of
progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...
. Several vaccines against human chorionic gonadotropin (hCG) for the prevention of pregnancy are currently in clinical trials.


Use in males

In males, hCG injections are used to stimulate the
Leydig cell Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...
s to synthesize
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
. The intratesticular testosterone is necessary for
spermatogenesis Spermatogenesis is the process by which haploid spermatozoa develop from germ cells in the seminiferous tubules of the testicle. This process starts with the Mitosis, mitotic division of the stem cells located close to the basement membrane of ...
from the
sertoli cells Sertoli cells are a type of sustentacular "nurse" cell found in human testes which contribute to the process of spermatogenesis (the production of sperm) as a structural component of the seminiferous tubules. They are activated by follicle-sti ...
. Typical medical uses for hCG in males include treating certain types of
hypogonadism Hypogonadism means diminished functional activity of the human gonad, gonads—the testicles or the ovary, ovaries—that may result in diminished biosynthesis, production of sex hormones. Low androgen (e.g., testosterone) levels are referred t ...
(either as monotherapy, or, more commonly, in combination with exogenous testosterone), as well as to either treat or prevent infertility, for example, during testosterone replacement therapy hCG is often used to restore or maintain fertility and prevent testicular atrophy.


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 In vitro fertilisation (IVF) is a process of fertilisation in which an egg is combined with sperm in vitro ("in glass"). The process involves monitoring and stimulating the ovulatory process, then removing an ovum or ova (egg or eggs) from ...
), are known to often be suffering from tubal abnormalities, after a treatment with this drug they might experience many more
ectopic pregnancies Ectopic pregnancy is a Complications of pregnancy, complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women ...
. 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 A multiple birth is the culmination of a multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such births ...
. 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 epilepsy might not be allowed to start using this medicine or may require a lower dose of HCG Pubergen, Pregnyl. This drug should be used with extreme caution in the treatment of
prepubescent Preadolescence is a stage of human development following middle childhood and preceding adolescence.New Oxford American Dictionary. 2nd Edition. 2005. Oxford University Press. It commonly ends with the beginning of puberty. Preadolescence is ...
teenagers in order to reduce the risk of 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 Pubergen, Pregnyl: (1) Hypersensitivity to this drug 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

HCG is included in some sports' banned substances lists. When exogenous AAS (Anabolic Androgenic Steroids) are put into the male body, natural negative-feedback loops cause the body to shut down its own production of
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
via shutdown of the hypothalamic-pituitary-gonadal axis ( HPGA). 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 The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
to shut down its production of
gonadotropin-releasing hormone Gonadotropin-releasing hormone (GnRH) is a releasing hormone responsible for the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary. GnRH is a tropic peptide hormone synthesized and rele ...
(GnRH) from the hypothalamus. Without GnRH, the
pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...
stops releasing
luteinizing hormone Luteinizing hormone (LH, also known as luteinising hormone, lutropin and sometimes lutrophin) is a hormone produced by gonadotropic cells in the anterior pituitary gland. The production of LH is regulated by gonadotropin-releasing hormone (G ...
(LH). LH normally travels from the pituitary via the blood stream to the testes, 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. Professional athletes who have tested positive for HCG have been temporarily banned from their sport, including a 50-game ban from
MLB Major League Baseball (MLB) is a professional baseball league composed of 30 teams, divided equally between the National League (baseball), National League (NL) and the American League (AL), with 29 in the United States and 1 in Canada. MLB i ...
for
Manny Ramirez Manuel Arístides Ramírez Onelcida (born May 30, 1972) is a Dominican Americans (Dominican Republic), Dominican-American former professional baseball outfielder. He played in Major League Baseball (MLB) for parts of 19 seasons. He played wit ...
in 2009 and a 4-game ban from the
NFL The National Football League (NFL) is a professional American football league in the United States. Composed of 32 teams, it is divided equally between the American Football Conference (AFC) and the National Football Conference (NFC). The N ...
for Brian Cushing for a positive urine test for HCG.
Mixed Martial Arts Mixed martial arts (MMA) is a full-contact fighting combat sport, sport based on strike (attack), striking and grappling; incorporating techniques from various combat sports from around the world. In the early 20th century, various inter-s ...
fighter
Dennis Siver Dennis D. Siver (Russian: Дмитрий Сивер, tr. Dmitriy Siver, born January 13, 1979) is a retired Russian-born German mixed martial artist who competed in the welterweight, lightweight, and featherweight division of the Ultimate Fighting ...
was fined $19,800 and suspended 9 months for being tested positive after his bout at
UFC 168 ''UFC 168: Weidman vs. Silva 2'' was a mixed martial arts event held on December 28, 2013, at the MGM Grand Garden Arena in Las Vegas, Nevada. Background The event was headlined by a UFC Middleweight Championship rematch between current champion ...
. Jurickson Profar tested positive for the substance and was suspended for 80-games on 3/31/2025.


HCG diet

British endocrinologist Albert T. W. Simeons proposed HCG as an adjunct to an ultra-low-calorie weight-loss diet (fewer than 500 calories). Simeons, while studying pregnant women in India on a calorie-deficient diet, and obese boys with pituitary issues ( Frölich's syndrome) treated with low-dose HCG, observed that both lost fat rather than lean (muscle) tissue. He reasoned that HCG must be programming the
hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...
to do this in the former cases in order to protect the developing fetus by promoting mobilization and consumption of ''abnormal'', ''excessive''
adipose Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...
deposits. Simeons in 1954 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, which was supposed to result in a loss of adipose tissue without loss of lean tissue. Other researchers did not find the same results when attempting experiments to confirm Simeons' conclusions, and in 1976 in response to complaints the FDA required Simeons and others to include the following disclaimer on all advertisements: There was a resurgence of interest in the "HCG diet" following promotion by
Kevin Trudeau Kevin Trudeau (; born ) is an American author, salesman, television personality, and convicted felon, known for promotion of his books and resulting legal cases involving the US Federal Trade Commission. His late-night infomercials, which prom ...
, who was banned from making HCG diet weight-loss claims by the U.S.
Federal Trade Commission The Federal Trade Commission (FTC) is an independent agency of the United States government whose principal mission is the enforcement of civil (non-criminal) United States antitrust law, antitrust law and the promotion of consumer protection. It ...
in 2008, and eventually jailed over such claims. A 1976 study in the American Journal of Clinical Nutrition concluded that HCG is not more effective as a weight-loss aid than dietary restriction alone. A 1995 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". On November 15, 2016, the
American Medical Association The American Medical Association (AMA) is an American professional association and lobbying group of physicians and medical students. This medical association was founded in 1847 and is headquartered in Chicago, Illinois. Membership was 271,660 ...
(AMA) passed policy that "The use of human chorionic gonadotropin (HCG) for weight loss is inappropriate." According to the American Society of Bariatric Physicians, no new clinical trials have been published since the definitive 1995 meta-analysis. The scientific consensus is that any weight loss reported by individuals on an "HCG diet" may be attributed entirely to the fact that such diets prescribe calorie intake of between 500 and 1,000 calories per day, substantially below recommended levels for an adult, to the point that this may risk health effects associated with malnutrition.


Homeopathic HCG for weight control

Controversy about, and shortages of, injected HCG for weight loss have led to substantial Internet promotion of "
homeopathic Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths or homeopathic physicians, believe that a substance tha ...
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. Moreover, it is highly unlikely that oral HCG is bioavailable due to the fact that digestive protease enzymes and hepatic metabolism renders peptide-based molecules (such as insulin and human growth hormone) biologically inert. HCG can likely only enter the bloodstream through injection. The United States
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
has stated that over-the-counter products containing HCG are fraudulent and ineffective for weight loss. They are also not protected as homeopathic drugs and have been deemed illegal substances. HCG is classified as a prescription drug in the United States and it has not been approved for over-the-counter sales by the FDA as a weight loss product or for any other purposes, and therefore neither HCG in its pure form nor any preparations containing HCG may be sold legally in the country except by prescription. In December 2011, FDA and FTC started to take actions to pull unapproved HCG products from the market. In the aftermath, some suppliers started to switch to "hormone-free" versions of their weight loss products, where the hormone is replaced with an unproven mixture of free amino acids or where
radionics Radionics—also called electromagnetic therapy (EMT) and the Abrams method—is a form of alternative medicine that claims that disease can be diagnosed and treated by applying electromagnetic radiation (EMR), such as radio waves, to the bod ...
is used to transfer the "energy" to the final product. , the United States
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...
has prohibited the sale of
homeopathic Homeopathy or homoeopathy is a pseudoscientific system of alternative medicine. It was conceived in 1796 by the German physician Samuel Hahnemann. Its practitioners, called homeopaths or homeopathic physicians, believe that a substance tha ...
and
over-the-counter Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs, which may be supplied only to consumers possessing a valid pres ...
hCG
diet Diet may refer to: Food * Diet (nutrition), the sum of the food consumed by an organism or group * Dieting, the deliberate selection of food to control body weight or nutrient intake ** Diet food, foods that aid in creating a diet for weight loss ...
products and declared them fraudelent and banned.


Tetanus vaccine conspiracy theory

Catholic Bishops in Kenya are among those who have spread a
conspiracy theory A conspiracy theory is an explanation for an event or situation that asserts the existence of a conspiracy (generally by powerful sinister groups, often political in motivation), when other explanations are more probable.Additional sources: * ...
asserting that HCG forms part of a covert sterilization program, forcing denials from the Kenyan government. In order to induce a stronger immune response, some versions of human chorionic gonadotropin-based anti-fertility vaccines were designed as conjugates of the β subunit of HCG covalently linked to
tetanus toxoid Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus. During childhood, five doses are recommended, with a sixth given during adolescence. After three doses, almost everyone is initially immune, but ...
. It was alleged that a non-conjugated
tetanus vaccine Tetanus vaccine, also known as tetanus toxoid (TT), is a toxoid vaccine used to prevent tetanus. During childhood, five doses are recommended, with a sixth given during adolescence. After three doses, almost everyone is initially immune, but ...
used in developing countries was laced with a human chorionic gonadotropin-based anti-fertility drug and was distributed as a means of mass sterilization. This charge has been vigorously denied by the
World Health Organization The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations which coordinates responses to international public health issues and emergencies. It is headquartered in Gen ...
(WHO) and
UNICEF UNICEF ( ), originally the United Nations International Children's Emergency Fund, officially United Nations Children's Fund since 1953, is an agency of the United Nations responsible for providing Humanitarianism, humanitarian and Development a ...
. Others have argued that an hCG-laced vaccine could not possibly be used for sterilization, since the effects of the anti-fertility vaccines are reversible (requiring
booster dose A booster dose is an extra administration of a vaccine after an earlier ( primer) dose. After initial immunization, a booster provides a re-exposure to the immunizing antigen. It is intended to increase immunity against that antigen back to prote ...
s to maintain infertility) and a non-conjugated vaccine is likely to be ineffective. Finally, independent testing of the tetanus vaccine by Kenya's health authorities revealed no traces of the human chorionic gonadotropin hormone.


See also

*
Equine chorionic gonadotropin Equinae is a subfamily of the family Equidae, known from the Hemingfordian stage of the Early Miocene (16 million years ago) onwards. They originated in North America, before dispersing to every continent except Australia and Antarctica. They ...
*
Gonadotropin preparations Gonadotropin preparations are drugs that mimic the physiological effects of gonadotropins, used therapeutically mainly as fertility medication for ovarian hyperstimulation and ovulation induction. For example, the so-called menotropins consist ...
*
Human placental lactogen Human placental lactogen (hPL), also called human chorionic somatomammotropin (hCS) or human chorionic somatotropin, is a polypeptide placental hormone, the human form of placental lactogen ( chorionic somatomammotropin). Its structure and fun ...
* Pregnancy hormones *
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 (and n ...
, a screening test in pregnancy * '' The Weight-Loss Cure "They" Don't Want You to Know About'', a book written by
Kevin Trudeau Kevin Trudeau (; born ) is an American author, salesman, television personality, and convicted felon, known for promotion of his books and resulting legal cases involving the US Federal Trade Commission. His late-night infomercials, which prom ...


References


External links

* * {{DEFAULTSORT:Human Chorionic Gonadotropin Genes on human chromosome 19 Glycoproteins Gynaecological endocrinology Peptide hormones Drugs developed by Schering-Plough Drugs developed by Merck & Co. Drugs developed by Merck Gonadotropin-releasing hormone and gonadotropins Hormones of the hypothalamus-pituitary-gonad axis Sex hormones Hormones of the placenta Hormones of the pregnant female Chemical pathology Tumor markers Anti-aging substances Tests for pregnancy Human female endocrine system