Anti-Müllerian hormone

anti-Müllerian hormone
Identifiers
Symbol	AMH
Entrez	268
HUGO	464
OMIM	600957
RefSeq	NM_000479
UniProt	P03971
Other data
Locus	Chr. 19 p13.3

anti-Mullerian hormone receptor, type II
Identifiers
Symbol	AMHR2
Entrez	269
HUGO	465
OMIM	600956
RefSeq	NM_020547
UniProt	Q16671
Other data
Locus	Chr. 12 q13

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.

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^[12] 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.^[13] 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^[14] and ovarian volume^[15].

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) ^[16][17] AMH can predict an excessive response in ovarian hyperstimulation with a sensitivity and specificity of 82% and 76%, respectively.^[18]

See also

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

References

1. ^ ^{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:10.1016/0092-8674(86)90783-X. PMID 3754790. http://linkinghub.elsevier.com/retrieve/pii/0092-8674(86)90783-X. 
2. ^ ^{a b} Behringer RR (1994). 5 The in Vivo Roles of Müllerian-inhibiting Substance. "The in vivo roles of müllerian-inhibiting substance". Curr. Top. Dev. Biol.. Current Topics in Developmental Biology 29: 171–87. doi:10.1016/S0070-2153(08)60550-5. ISBN 9780121531294. PMID 7828438. 
3. ^ 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:10.1038/ng1295-382. PMID 7493017. 
4. ^ Page 1114 in: Walter F., PhD. Boron (2003). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. pp. 1300. ISBN 1-4160-2328-3. 
5. ^ An Introduction to Behavioral Endocrinology, Randy J Nelson, 3rd edition, Sinauer
6. ^ Kelsey TW, Wright P, Nelson SM,Anderson RA, Wallace WHB (2011). "A validated model of serum anti-Müllerian hormone from conception to menopause". PLoS ONE 6 (7). doi:10.1371/journal.pone.0022024. PMC 3137624. PMID 21789216. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022024. 
7. ^ 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:10.1093/molehr/gah015. PMID 14742691. http://molehr.oxfordjournals.org/cgi/content/abstract/10/2/77. 
8. ^ Broer SJ at al (2011). "Anti-müllerian hormone predicts menopause: a long-term follow-up study in normoovulatory women". J Clin Endocrinol Metab 96 (8). 
9. ^ 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:10.1530/rep.1.00529. PMID 16388003. http://www.reproduction-online.org/cgi/content/full/131/1/1. 
10. ^ 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:10.1016/j.jsbmb.2004.07.002. PMID 15555913. 
11. ^ 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:10.1073/pnas.0902253106. PMC 2678437. PMID 19359476. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2678437. 
12. ^ Kelsey TW, Wright P, Nelson SM, Anderson RA, Wallace WHB (2011). "A validated model of serum anti-Müllerian hormone from conception to menopause". PLoS ONE 6 (7). doi:10.1371/journal.pone.0022024. PMC 3137624. PMID 21789216. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0022024. 
13. ^ 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. 
14. ^ 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:10.1016/j.fertnstert.2007.02.014. PMID 17559842. http://linkinghub.elsevier.com/retrieve/pii/S0015-0282(07)00352-4. 
15. ^ Wallace WHB, Kelsey TW (2004). "Ovarian reserve and reproductive age may be determined from measurement of ovarian volume by transvaginal sonography.". Human Reproduction 19 (7). doi:10.1093/humrep/deh285. PMID 15205396. http://humrep.oxfordjournals.org/content/19/7/1612.long. 
16. ^ Nelson SM, Yates RW et al. (2007). "Serum anti-Mullerian hormone and FSH: prediction of live birth and extremes of response in stimulated cycles—implications for individualization of therapy". Human Reproduction 22 (9): 2414–2421. doi:10.1093/humrep/dem204. PMID 17636277. 
17. ^ Nelson SM, Yates RW et al. (2009). "Anti-Mullerian hormone-based approach to controlled ovarian stimulation for assisted conception". Human Reproduction 1 (1): 1–9. 
18. ^ Broer, S. L.; Dolleman, M.; Opmeer, B. C.; Fauser, B. C.; Mol, B. W.; Broekmans, F. J. M. (2010). "AMH and AFC as predictors of excessive response in controlled ovarian hyperstimulation: a meta-analysis". Human Reproduction Update 17 (1): 46. doi:10.1093/humupd/dmq034. PMID 20667894.  edit