Anti-Müllerian hormone type-2 receptor

AMHR2 belongs to TGF-β type II receptor family, a protein receptor on the surface of sells. Structurally it adopts the characteristic three-finger toxin fold, such that the outer portion of the receptor resembles three fingers. It displays a unique extended finger-1 loop, critical to signaling the AMH molecule. The palm region and other fingers are also necessary for the process of binding to the ligand, AMH. But these structures are relatively unremarkable when compared to other TGF-β type II receptors.^[7] As such, these interactions do not contribute significantly to the observed ligand specificity for AMH, it is primarily the uniqueness of the finger-1 loop which allows it to bind.^[6]

The gene is present in both men and women, because it is found in an autosome, one of the twenty two non-sex chromosomes pairs carried by humans.^[8] The AMHR2 is a Type II receptor that binds AMH. This hormone is responsible for Müllerian Duct regression in vertebrates once the SRY gene - the protein involved in sexual development of males - has been expressed.^[9]

Some animals, such as jawless fish, do not express either AMH or its receptors.^[10] High circulating AMH, pr the continual presence of AMH in the bloodstream, continues on after testis development and is secreted from the Sertoli cells.^[11] It is also expressed in Leydig cells.^[12] It has been reported that the loss of function of the AMHR2 gene results in 50% of XY animals experiencing a sex reversal from male to female. The loss of the protein's functionality has also led to hyper-proliferation of mitotically active germ cells, which leads to the sex reversal.^[10] AMH binding to the AMHR2 in mammals causes regression of the oviducts, uterus, and upper two thirds of the vagina.^[13][14]

AMHR2 is expressed by ovarian, breast, and prostate cancers. These cancer cells have been reported to apoptose in response to exposure to the Müllerian inhibiting substance (MIS).^[15]

Monoclonal antibodies have also been developed that specifically target MISIIR and may be useful as vehicles for drugs and toxins for targeted cancer therapy.^[16][17][18]

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.^[19] The results are such that males may retain tissues normally eliminated during development. 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 as a result of having fewer antral follicles. This causes more atresia, or closing, of the follicles prior to developing an antrum. These phenotypes were confirmed to be the cause of an AMHR2 mutation from resulting studies performed in mice.^[20]

• Autosome
• Chromosome 12
• Intersex