Anti-müllerian hormone
Encyclopedia
Anti-Müllerian hormone also known as AMH is a protein
that, in humans, is encoded by the AMH gene
. It inhibits the development of the Müllerian duct
s (paramesonephric ducts) in the male embryo
. It has also been called Müllerian inhibiting factor (MIF), Müllerian-inhibiting hormone (MIH), and Müllerian-inhibiting substance (MIS). It is named after Johannes Peter Müller
.
, reptile
s, bird
s, marsupial
s, and placental mammal
s.
s of the testes during embryogenesis
of the fetal male.
hormone
structurally related to inhibin and activin, and a member of the transforming growth factor-β (TGF-β) family. It is a dimeric
glycoprotein
.
for AMH is AMH, on chromosome
19p13.3, while the gene codes for its receptor
on chromosome
12.
s into the uterus
and other mullerian structures. The effect is ipsilateral, that is each testis suppresses Müllerian development only on its own side. In humans, this action takes place during the first 8 weeks of gestation. If no hormone is produced from the gonads, the Mullerian ducts automatically develop, while the Wolffian ducts, which are responsible for male reproductive ducts, automatically die.
Amounts of AMH that are measurable in the blood vary by age and sex. AMH works by interacting with specific receptor
s on the surfaces of the cells of target tissues. The best-known and most specific effect, mediated through the AMH type II receptors, includes programmed cell death (apoptosis
) of the target tissue (the fetal mullerian ducts).
; from 25 years of age AMH declines to undetectable levels at menopause. AMH is expressed by granulosa cells of the ovary
during the reproductive years, and controls the formation of primary follicles by inhibiting excessive follicular recruitment by FSH. It, therefore, has a role in folliculogenesis, and some authorities suggest it is a measure of certain aspects of ovarian function, useful in assessing conditions such as polycystic ovary syndrome
and premature ovarian failure
.
s of the testes remains high throughout childhood in males but declines to low levels during puberty and adult life. AMH has been shown to regulate production of sex hormones, and changing AMH levels (falling in females, rising in males) may be involved in the onset of puberty in both sexes. Functional AMH receptors have also been found to be expressed on neurons in the brains of embryonic mice, and are thought to play a role in sexually dimorphic
brain development and consequent development of gender-specific behaviours.
(PMDS), in which a rudimentary uterus is present and testes are usually undescended
. The AMH gene (AMH) or the gene (AMH-RII) for its receptor are usually abnormal. AMH measurements have also become widely used in the evaluation of testicular presence and function in infants with intersex
conditions, ambiguous genitalia, and cryptorchidism
.
, adenomyosis
, and uterine cancer
. Research is underway in several laboratories.
Comparison of an individual's AMH level with respect to average levels is also useful in fertility assessment, as it provides a guide to ovarian reserve
and identifies women that may need to consider either egg freezing or trying for a pregnancy sooner rather than later if their long-term future fertility is poor. Measuring AMH alone may be misleading as high levels occur in conditions like polycystic ovarian syndrome and therefore AMH levels should be considered in conjunction with a transvaginal scan
of the ovaries to assess antral follicle count and ovarian volume.
It also has the potential to rationalise the programme of ovulation induction and decisions about the number of embryos to transfer in assisted reproduction techniques to maximise pregnancy success rates whilst minimising the risk of ovarian hyperstimulation syndrome
(OHSS) AMH can predict an excessive response in ovarian hyperstimulation with a sensitivity and specificity
of 82% and 76%, respectively.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that, in humans, is encoded by the AMH 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...
. It inhibits the development of the Müllerian duct
Müllerian duct
Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in...
s (paramesonephric ducts) in the male 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...
. It has also been called Müllerian inhibiting factor (MIF), Müllerian-inhibiting hormone (MIH), and Müllerian-inhibiting substance (MIS). It is named after Johannes Peter Müller
Johannes Peter Müller
Johannes Peter Müller , was a German physiologist, comparative anatomist, and ichthyologist not only known for his discoveries but also for his ability to synthesize knowledge.-Early years and education:...
.
Species distribution
AMH is present in fishFish
Fish are a paraphyletic group of organisms that consist of all gill-bearing aquatic vertebrate animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish, as well as various extinct related groups...
, reptile
Reptile
Reptiles are members of a class of air-breathing, ectothermic vertebrates which are characterized by laying shelled eggs , and having skin covered in scales and/or scutes. They are tetrapods, either having four limbs or being descended from four-limbed ancestors...
s, bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s, marsupial
Marsupial
Marsupials are an infraclass of mammals, characterized by giving birth to relatively undeveloped young. Close to 70% of the 334 extant species occur in Australia, New Guinea, and nearby islands, with the remaining 100 found in the Americas, primarily in South America, but with thirteen in Central...
s, and placental mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s.
Source
AMH is secreted by Sertoli cellSertoli cell
A Sertoli cell is a 'nurse' cell of the testes that is part of a seminiferous tubule.It is activated by follicle-stimulating hormone and has FSH-receptor on its membranes.-Functions:...
s of the testes during embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
of the fetal male.
Structure
AMH is a proteinProtein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
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...
structurally related to inhibin and activin, and a member of the transforming growth factor-β (TGF-β) family. It is a dimeric
Protein dimer
In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules like proteins or nucleic acids...
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...
.
Gene
In humans, the geneGene
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...
for AMH is AMH, on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
19p13.3, while the gene codes for its receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
12.
Embryogenesis
In mammals, AMH prevents the development of the mullerian ductMüllerian duct
Müllerian ducts are paired ducts of the embryo that run down the lateral sides of the urogenital ridge and terminate at the Müllerian eminence in the primitive urogenital sinus. In the female, they will develop to form the Fallopian tubes, uterus, cervix, and the upper two-third of the vagina; in...
s into 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...
and other mullerian structures. The effect is ipsilateral, that is each testis suppresses Müllerian development only on its own side. In humans, this action takes place during the first 8 weeks of gestation. If no hormone is produced from the gonads, the Mullerian ducts automatically develop, while the Wolffian ducts, which are responsible for male reproductive ducts, automatically die.
Amounts of AMH that are measurable in the blood vary by age and sex. AMH works by interacting with specific receptor
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
s on the surfaces of the cells of target tissues. The best-known and most specific effect, mediated through the AMH type II receptors, includes programmed cell death (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...
) of the target tissue (the fetal mullerian ducts).
Ovarian
In healthy females AMH is either just detectable or undetectable in cord blood at birth and demonstrates a marked rise by three months of age; while still detectable it falls until four years of age before rising linearly until eight years of age remaining fairly constant from mid-childhood to early adulthood - it does not change significantly during pubertyPuberty
Puberty is the process of physical changes by which a child's body matures into an adult body capable of reproduction, as initiated by hormonal signals from the brain to the gonads; the ovaries in a girl, the testes in a boy...
; from 25 years of age AMH declines to undetectable levels at menopause. AMH is expressed by granulosa cells of the ovary
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...
during the reproductive years, and controls the formation of primary follicles by inhibiting excessive follicular recruitment by FSH. It, therefore, has a role in folliculogenesis, and some authorities suggest it is a measure of certain aspects of ovarian function, useful in assessing conditions such as polycystic ovary syndrome
Polycystic ovary syndrome
Polycystic ovary syndrome is one of the most common female endocrine disorders. PCOS is a complex, heterogeneous disorder of uncertain aetiology, but there is strong evidence that it can to a large degree be classified as a genetic disease....
and premature ovarian failure
Premature ovarian failure
Premature Ovarian Failure , also known as premature ovarian insufficiency, primary ovarian insufficiency , premature menopause, hypergonadotropic hypogonadism, is the loss of function of the ovaries before age 40...
.
Other
AMH production by the Sertoli cellSertoli cell
A Sertoli cell is a 'nurse' cell of the testes that is part of a seminiferous tubule.It is activated by follicle-stimulating hormone and has FSH-receptor on its membranes.-Functions:...
s of the testes remains high throughout childhood in males but declines to low levels during puberty and adult life. AMH has been shown to regulate production of sex hormones, and changing AMH levels (falling in females, rising in males) may be involved in the onset of puberty in both sexes. Functional AMH receptors have also been found to be expressed on neurons in the brains of embryonic mice, and are thought to play a role in sexually dimorphic
Sexual dimorphism
Sexual dimorphism is a phenotypic difference between males and females of the same species. Examples of such differences include differences in morphology, ornamentation, and behavior.-Examples:-Ornamentation / coloration:...
brain development and consequent development of gender-specific behaviours.
Pathology
In men, inadequate embryonal AMH activity can lead to the Persistent Müllerian duct syndromePersistent Mullerian duct syndrome
Persistent Müllerian duct syndrome refers to the presence of a uterus and sometimes other Müllerian duct derivatives in a male animal...
(PMDS), in which a rudimentary uterus is present and testes are usually undescended
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
. The AMH gene (AMH) or the gene (AMH-RII) for its receptor are usually abnormal. AMH measurements have also become widely used in the evaluation of testicular presence and function in infants with intersex
Intersex
Intersex, in humans and other animals, is the presence of intermediate or atypical combinations of physical features that usually distinguish female from male...
conditions, ambiguous genitalia, and cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
.
Application
AMH has been synthesized. Its ability to inhibit growth of tissue derived from the Müllerian ducts has raised hopes of usefulness in the treatment of a variety of medical conditions including endometriosisEndometriosis
Endometriosis is a gynecological medical condition in which cells from the lining of the uterus appear and flourish outside the uterine cavity, most commonly on the ovaries. The uterine cavity is lined by endometrial cells, which are under the influence of female hormones...
, adenomyosis
Adenomyosis
Adenomyosis is a medical condition characterized by the presence of ectopic glandular tissue found in muscle. The term adenomyosis is derived from the terms adeno- , myo- , and -osis...
, and uterine 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...
. Research is underway in several laboratories.
Comparison of an individual's AMH level with respect to average levels is also useful in fertility assessment, as it provides a guide to ovarian reserve
Ovarian reserve
Ovarian reserve is a term that is used to determine the capacity of the ovary to provide eggs that are capable of fertilization resulting in a healthy and successful pregnancy...
and identifies women that may need to consider either egg freezing or trying for a pregnancy sooner rather than later if their long-term future fertility is poor. Measuring AMH alone may be misleading as high levels occur in conditions like polycystic ovarian syndrome and therefore AMH levels should be considered in conjunction with a transvaginal scan
Obstetric ultrasonography
Obstetric sonography is the application of medical ultrasonography to obstetrics, in which sonography is used to visualize the embryo or foetus in its mother's uterus...
of the ovaries to assess antral follicle count and ovarian volume.
It also has the potential to rationalise the programme of ovulation induction and decisions about the number of embryos to transfer in assisted reproduction techniques to maximise pregnancy success rates whilst minimising the risk of ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome
Ovarian hyperstimulation syndrome is a complication from some forms of fertility medication. Most cases are mild, but a small proportion are severe.-Causative medications:...
(OHSS) AMH can predict an excessive response in ovarian hyperstimulation with a sensitivity and specificity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...
of 82% and 76%, respectively.
See also
- Sexual differentiationSexual differentiationSexual differentiation is the process of development of the differences between males and females from an undifferentiated zygote...
- Anti-Mullerian hormone receptorAnti-Mullerian hormone receptorAnti-Müllerian hormone receptor is a receptor for anti-Müllerian hormone.-Pathology:The anti-Mullerian hormone receptor can be responsible for persistent Müllerian duct syndrome.-External links:...
- Alfred JostAlfred JostAlfred Jost was a French endocrinologist, famous for his discovery of the Mullerian inhibitor, now called anti-Mullerian hormone or Mullerian inhibiting substance...
discoverer. - PMDS (Persistent Mullerian Duct Syndrome)