AMHR2 - Anti-Muellerian hormone type-2 receptor | Reagents (Elisa - Clia - Antibody - Protein

Background:

The Anti-Müllerian hormone (AMH) type-2 receptor, also known as AMHR2, plays a crucial role in the Müllerian duct regression during male fetal development. Müllerian ducts are the embryonic precursors to the female reproductive tract (uterus, fallopian tubes, cervix), and AMHR2 helps in the regression of these ducts in males, allowing for the development of the male reproductive system instead. AMH itself is a protein hormone produced by cells in developing testicles, and its binding to AMHR2 triggers the regression of the Müllerian ducts. Mutations in the AMHR2 gene can lead to disorders of sex development (DSD), affecting the development of the reproductive system. This receptor is also implicated in ovarian function in females. AMHR2 is a transmembrane serine/threonine kinase receptor, belonging to the TGF-beta receptor family. In males, it's found in the testes where it plays a crucial role in the development of male reproductive organs. In females, AMHR2 is expressed in the ovaries, specifically in granulosa cells of developing follicles. In males, the Müllerian ducts need to regress to allow for the development of the male reproductive system (seminal vesicles, epididymis, vas deferens). AMHR2 facilitates this regression. AMH (Anti-Müllerian hormone) secreted by Sertoli cells in the testes binds to AMHR2 on the Müllerian ducts, causing them to regress. In females, AMHR2 is involved in folliculogenesis, the process of ovarian follicle development. High levels of AMHR2 are found in granulosa cells surrounding developing ovarian follicles. AMH signaling through AMHR2 helps to regulate the number of primordial follicles that develop into larger, more mature follicles.

Protein Structure:

• Molecular Weight: Approximately 60-70 kDa.
• Domains: AMHR2 is a transmembrane serine/threonine kinase receptor. It consists of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular kinase domain.
• Post-translational Modifications: AMHR2 undergoes glycosylation, which is essential for its proper function and interaction with AMH.

Classification and Subtypes:

• Family: AMHR2 is a member of the TGF-β receptor family, which includes various receptors that mediate the effects of TGF-β superfamily ligands.
• Subtypes: AMHR2 itself does not have distinct subtypes, but it functions as part of a receptor complex that includes type I receptors, such as ALK2, ALK3, and ALK6.

Function and Biological Significance:

• Sexual Differentiation: In males, AMHR2 mediates the effect of AMH produced by Sertoli cells, leading to the regression of Müllerian ducts, thus preventing the development of female reproductive organs.
• Ovarian Function: In females, AMHR2 is expressed in granulosa cells of the ovaries and is involved in folliculogenesis. It modulates the effects of AMH on follicle recruitment and sensitivity to FSH.
• Regulatory Role: AMHR2, through its interaction with AMH, plays a role in inhibiting the initial recruitment of primordial follicles, thereby regulating the ovarian reserve.

Interactions:

• AMH Binding: AMHR2 specifically binds to AMH, initiating the signaling cascade required for Müllerian duct regression and ovarian function regulation.
• Receptor Complex Formation: Upon AMH binding, AMHR2 recruits type I receptors (such as ALK2, ALK3, and ALK6), which phosphorylate and activate SMAD proteins, leading to the transcriptional regulation of target genes.
• TGF-β Pathways: The signaling mechanisms of AMHR2 overlap with other TGF-β family members, involving SMAD-dependent and SMAD-independent pathways.

Clinical Issues:

• Persistent Müllerian Duct Syndrome (PMDS): Mutations in the AMHR2 gene can result in PMDS, a condition where males develop both male and female reproductive structures due to the failure of Müllerian duct regression.
• Ovarian Disorders: Abnormal AMHR2 function or expression can affect ovarian reserve and fertility. Alterations in AMHR2 signaling are implicated in conditions like PCOS and premature ovarian insufficiency.
• Cancer: AMHR2 expression has been explored as a therapeutic target in certain cancers, including ovarian and prostate cancers, due to its role in cell proliferation and differentiation.

Summary:

AMHR2 is a crucial receptor in the AMH signaling pathway, playing a significant role in sexual differentiation and ovarian function. It is a transmembrane receptor that mediates the regression of Müllerian ducts in males and regulates folliculogenesis in females. Mutations or dysregulation of AMHR2 can lead to disorders such as PMDS and affect ovarian health and fertility. Understanding the function and interactions of AMHR2 provides insights into its potential therapeutic applications in reproductive health and oncology.