Genomic coordinate (human 12:53,423,855 AMHR2).
Cytoband (human 12q13.13 AMHR2).
Intraband % = 69.3%
Here I present: “Anti-Mullerian Hormone Receptor-2″, Victor McKusick, Mendelian Inheritance in Man’, 1966. idc10=Q55.8 (AMHR2)
The persistent Mullerian duct syndrome type-2 is characterized by the persistence of Mullerian derivatives, uterus and tubes, in otherwise normally virilized males.
Typical persistent Müllerian duct syndrome case is that of a male with bilateral cryptorchidism and inguinal hernias but normal male external genitalia otherwise. At the time of hernia repair, a uterus and fallopian tubes are found in the inguinal canal. The gonads are testes.
The Anti-Müllerian Hormone Receptor Type 2 (AMHR2)—also known as the Müllerian inhibiting substance type II receptor—is the primary transmembrane protein that binds exclusively to Anti-Müllerian Hormone (AMH). This receptor is a single-transmembrane serine/threonine kinase belonging to the Transforming Growth Factor-beta TGF-beta type II receptor family. It plays an indispensable role in embryonic sex differentiation in males and ovarian follicle development in females.
Signaling Mechanism.
The AMH signaling cascade operates as a multi-protein unit:
Ligand Binding: Free AMH binds directly to the extracellular domain of the type II receptor (AMHR2).
Receptor Recruitment: Once bound, AMHR2 recruits a type I receptor (such as BMPR-IB).
Downstream Activation: AMHR2 phosphorylates the type I receptor, triggering intracellular signaling via cytoplasmic Smad1/5/8 proteins to alter gene transcription.
Physiological Roles
Male Embryonic Development: In male fetuses, the testes secrete AMH. The hormone binds to AMHR2 on the surface of the Müllerian duct cells, signaling programmed cell death (apoptosis). This regresses the tissues that would otherwise form the uterus and fallopian tubes.
Female Postnatal Reproduction:
In adult females, AMHR2 is expressed by the granulosa cells of growing ovarian follicles. It acts as a follicular gatekeeper by inhibiting the premature recruitment of primordial follicles and reducing follicle sensitivity to Follicle-Stimulating Hormone (FSH).
Extragonadal Functions: Modern endocrinology indicates that AMHR2 is also expressed in the brain (hypothalamus and anterior pituitary), where it helps regulate the secretion of gonadotropins like LH and FSH.
Clinical Significance & Mutations.
Persistent Müllerian Duct Syndrome (PMDS): Genetic mutations in the human AMHR2 gene (located on chromosome 12q13.13) cause Persistent Müllerian Duct Syndrome Type II. This autosomal recessive condition results in normal, virilized phenotypic males who internally retain a uterus and fallopian tubes.
Polycystic Ovary Syndrome (PCOS): Women with PCOS frequently exhibit an overexpression of both AMH and AMHR2 in their ovarian granulosa cells. This overexpression contributes to the arrested follicle development and ovulation difficulties characteristic of the syndrome.
There is evidence that persistent Müllerian duct syndrome type-2 (PMDS) is caused by mutation in the anti-Mullerian hormone receptor-2 (AMHR2) gene encoded on genomic coordinate 12:53,423,855 and cytoband 12q13.13 in humans.
