Anti-Müllerian hormone
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Anti-Müllerian hormone also known as AMH is a protein which in humans is encoded by the AMH gene.[1] 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.
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[edit] Species distribution
AMH is present in fish, reptiles, birds, marsupials, and placental mammals.
[edit] Function
AMH is a protein hormone structurally related to inhibin and activin, and a member of the transforming growth factor-β (TGF-β) family. AMH is a dimeric glycoprotein that inhibits the development of the Müllerian ducts in the male embryo.[2]
[edit] 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]
[edit] Function
[edit] Embryogenesis
In mammals AMH is secreted by Sertoli cells of the testes during embryogenesis of the fetal male and 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. In humans this action takes place by 8 weeks gestation. In female embryogenesis the absence of AMH allows for the development of upper vagina, uterus and cervix, and oviducts. 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).
[edit] Ovarian
While AMH is measurable in males during childhood and adulthood, AMH cannot be detected in women until puberty. AMH is expressed by granulosa cells of the ovary in the reproductive age and controls the formation of primary follicles by inhibiting excessive follicular recruitment by FSH. It therefore has a role in folliculogenesis,[4] and some authorities suggest it is a measure of some aspects of ovarian function useful in assessing conditions such as polycystic ovary syndrome and premature ovarian failure.[5]
[edit] 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,[6] and changing AMH levels (falling in males, rising in females) 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 diamorphic brain development and consequent development of gender-specific behaviours.[7]
[edit] 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.
[edit] 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.
AMH assessment is also useful in fertility assessment as it provides a guide to ovarian reserve and identifies women who may need to consider either egg freezing or trying for a pregnancy sooner rather than later if their long term future fertility is poor.[8] 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.[9]
[edit] See also
- Sexual differentiation
- anti-Mullerian hormone receptor
- Alfred Jost discoverer.
- PMDS (Persistant Mullerian Duct Syndrome)
[edit] Footnotes
- ^ a b Cate RL, Mattaliano RJ, Hession C, Tizard R, Farber NM, Cheung A, Ninfa EG, Frey AZ, Gash DJ, Chow EP (June 1986). "Isolation of the bovine and human genes for Müllerian inhibiting substance and expression of the human gene in animal cells". Cell 45 (5): 685–98. doi:. PMID 3754790. http://linkinghub.elsevier.com/retrieve/pii/0092-8674(86)90783-X.
- ^ a b Behringer RR (1994). "The in vivo roles of müllerian-inhibiting substance". Curr. Top. Dev. Biol. 29: 171–87. doi:. PMID 7828438.
- ^ Imbeaud S, Faure E, Lamarre I, Mattéi MG, di Clemente N, Tizard R, Carré-Eusèbe D, Belville C, Tragethon L, Tonkin C, Nelson J, McAuliffe M, Bidart JM, Lababidi A, Josso N, Cate RL, Picard JY (December 1995). "Insensitivity to anti-müllerian hormone due to a mutation in the human anti-müllerian hormone receptor". Nat. Genet. 11 (4): 382–8. doi:. PMID 7493017.
- ^ Weenen C, Laven J, Von Bergh A, Cranfield M, Groome N, Visser J, Kramer P, Fauser B, Themmen A (2004). "Anti-Müllerian hormone expression pattern in the human ovary: potential implications for initial and cyclic follicle recruitment" (abstract). Mol Hum Reprod 10 (2): 77–83. doi:. PMID 14742691. http://molehr.oxfordjournals.org/cgi/content/abstract/10/2/77.
- ^ Visser J, de Jong F, Laven J, Themmen A (2006). "Anti-Müllerian hormone: a new marker for ovarian function". Reproduction 131 (1): 1–9. doi:. PMID 16388003. http://www.reproduction-online.org/cgi/content/full/131/1/1.
- ^ Trbovich AM, Martinelle N, O'Neill FH, Pearson EJ, Donahoe PK, Sluss PM, Teixeira J (October 2004). "Steroidogenic activities in MA-10 Leydig cells are differentially altered by cAMP and Müllerian inhibiting substance". The Journal of Steroid Biochemistry and Molecular Biology 92 (3): 199–208. doi:. PMID 15555913.
- ^ Wang PY, Protheroe A, Clarkson AN, Imhoff F, Koishi K, McLennan IS (April 2009). "Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior". Proceedings of the National Academy of Sciences of the United States of America 106 (17): 7203–8. doi:. PMID 19359476.
- ^ Cupisti S, Dittrich R, Mueller A, Strick R, Stiegler E, Binder H, Beckmann MW, Strissel P (December 2007). "Correlations between anti-müllerian hormone, inhibin B, and activin A in follicular fluid in IVF/ICSI patients for assessing the maturation and developmental potential of oocytes". Eur. J. Med. Res. 12 (12): 604–8. PMID 18024272.
- ^ Seifer DB, Maclaughlin DT (September 2007). "Mullerian Inhibiting Substance is an ovarian growth factor of emerging clinical significance". Fertil. Steril. 88 (3): 539–46. doi:. PMID 17559842. http://linkinghub.elsevier.com/retrieve/pii/S0015-0282(07)00352-4.
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