Anti-Müllerian hormone

Anti-Müllerian hormone also known as AMH is a protein that, in humans, is encoded by the AMH gene.^[1] It inhibits the development of the Müllerian ducts (paramesonephric ducts) in the male embryo.^[2] 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.

Species distribution

AMH is present in fish, reptiles, birds, marsupials, and placental mammals.

Source

AMH is secreted by Sertoli cells of the testes during embryogenesis of the fetal male.

Structure

AMH is a protein hormone structurally related to inhibin and activin, and a member of the transforming growth factor-β (TGF-β) family. It is a dimeric glycoprotein.

Gene

In humans, the gene for AMH is AMH, on chromosome 19p13.3,^[1] while the gene AMHR2 codes for its receptor on chromosome 12.^[3]

Function

Embryogenesis

In mammals, AMH prevents the development of the mullerian ducts into the uterus and other mullerian structures.^[2] The effect is ipsilateral, that is each testis suppresses Müllerian development only on its own side.^[4] 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.^[5] Amounts of AMH that are measurable in the blood vary by age and sex. AMH works by interacting with specific receptors 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).

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 puberty; from 25 years of age AMH declines to undetectable levels at menopause.^[6] 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,^[7] and some authorities suggest it is a measure of certain aspects of ovarian function^[8], useful in assessing conditions such as polycystic ovary syndrome and premature ovarian failure.^[9]

Other

AMH production by the Sertoli cells 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,^[10] 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.^[11]

Pathology

In men, inadequate embryonal AMH activity can lead to the Persistent Müllerian duct syndrome (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.

Reference ranges

Reference ranges for Anti-Müllerian hormone, as estimated from reference groups in the United states, are as follows:^[12]

Females:

• Younger than 24 months: Less than 5 ng/mL
• 24 months to 12 years: Less than 10 ng/mL
• 13-45 years: 1 to 10 ng/mL
• More than 45 years: Less than 1 ng/mL

Males:

• Younger than 24 months: 15 to 500 ng/mL
• 24 months to 12 years: 7 to 240 ng/mL
• More than 12 years: 0.7 to 20 ng/mL

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 endometriosis, adenomyosis, and uterine cancer. Research is underway in several laboratories.

Comparison of an individual's AMH level with respect to average levels^[13] 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.^[14] 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^[15] and ovarian volume^[16].

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) ^[17][18] AMH can predict an excessive response in ovarian hyperstimulation with a sensitivity and specificity of 82% and 76%, respectively.^[19]

See also

• Sexual differentiation
• Anti-Mullerian hormone receptor
• Alfred Jost discoverer.
• PMDS (Persistent Müllerian Duct Syndrome)

References