Anti-Müllerian Hormone Receptor

Anti-Müllerian hormone receptor, also known as Müllerian Inhibiting Substance Type II Receptor, is a receptor for the anti-Müllerian hormone (AMH). Furthermore, anti-Müllerian hormone receptor type 2 is a protein in humans that is encoded by the AMHR2 gene.

Structure

AMHR2 belongs to TGF-β type II receptor family and adopts the characteristic three-finger toxin fold. However, it displays a unique extended finger 1 loop (see image) that is critical to effectively binding its ligand, AMH. The palm region and other fingers are also implicated in binding to AMH, but are relatively unremarkable when compared to other TGF-β type II receptors. As such, these interactions do not contribute significantly to the observed ligand specificity for AMH like the finger 1 loop.

Function

The gene is present in both men and women. AMHR2 is a Type 2 receptor that binds AMH (Anti-Müllerian hormone). This hormone is responsible for Müllerian Duct regression in vertebrates once the SRY gene has been expressed. Some animals such as jawless fish do not express either AMH or its receptors. High circulating AMH continues on after testis development and is secreted from the Sertoli Cells. It is also expressed in Leydig cells. It has been reported that the loss of function of the AMHR2 gene results in 50% of XY animals to reverse sex to females and also leads to hyperproliferation of mitotically active germ cells, which leads to the sex reversal. AMH binding to the AMHR2 in mammals causes regression of the oviducts, uterus, and upper 2/3 of the vagina.

Clinical significance

Müllerian inhibiting substance type II receptor (MISIIR), also known as the Anti-Müllerian Hormone Receptor, is expressed by ovarian, breast, and prostate cancers and these cancer cells have been reported to apoptose in response to exposure to the Müllerian inhibiting substance (MIS).

Monoclonal Antibodies have been developed that specifically target MISIIR and may be useful as vehicles for drugs and toxins for targeted cancer therapy.

A syndrome called "Persistent Mullerian Duct Syndrome" (PMDS) can occur in human males and results in the uterus, vagina, and uterus being present in virilized male. PMDS can be caused by a genetic mutation of deletions, or missenses, and these males often have undescended testes or cryptorchidism, where one testis fails to descend outside of the body cavity. The majority of these patients will be infertile. In females that are homozygous for the mutation, no abnormalities have been observed. However, heterozygous females have been observed to reach menopause sooner and display a lowered AMH level which also is an indicator of antral follicle count. It is likely that these females reach menopause sooner from having fewer antral follicles, thus more atresia of follicles prior to developing an antrum. These phenotypes were confirmed to be the cause of an AMHR2 mutation from knock out studies performed in mice.

References

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Further reading

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{{DEFAULTSORT:Anti-Mullerian hormone receptor
EC 2.7.11