Disease relevance of AMH

• Finally, AMH determination on the seminal plasma of men with non-obstructive azoospermia may be used as a marker of the existence of testicular spermatozoa when intracytoplasmic sperm injection is considered [1].
• Serum AMH is a useful marker in the follow-up of male patients with precocious puberty or hypogonadotrophic hypogonadism, as well as of patients with sex cord stromal tumours of the gonads [1].
• In addition to causing regression of the Mullerian duct in the male embryo, Mullerian Inhibiting Substance (MIS) inhibits the growth of epithelial ovarian cancer cells, which are known to be of Mullerian origin [2].
• A number of cervical cancer cell lines express the MIS type II receptor, and MIS inhibits the growth of both human papilloma virus-transformed and non-human papilloma virus-transformed cervical cell lines, with a more dramatic effect seen in the latter [2].
• AMH immunoreactivity was conserved in premeiotic seminiferous tubules of dysgenetic testes, and also in sex-cord cells of a gonadoblastoma [3].

Psychiatry related information on AMH

• This population is suitable to test the influence of an absence of androgens and Müllerian inhibiting substance on psychosexual development in genetic males [4].
• Pain thresholds in normal skin were matched only by the response thresholds of CMH and not AMH nociceptors [5].
• Secretion of AMH begins shortly after testicular differentiation and lasts into the perinatal period; however, the müllerian duct is responsive to AMH only during a short "critical" period at the end of the ambisexual stage [6].
• The present study was designed to investigate a variety of visual deficits reported by children who experience high levels of visual stress and perceptual distortions when reading (Meares-Irlen syndrome; MIS) and to assess the improvements in visual comfort they report when tinted lenses are worn [7].
• Psychometric functions also revealed no significant difference between subject groups (control versus MIS) [7].

High impact information on AMH

• Here, we show that WT1 -KTS isoforms associate and synergize with SF-1 to promote MIS expression [8].
• In males, SF-1 participates in sexual development by regulating expression of the polypeptide hormone Müllerian inhibiting substance (MIS) [8].
• BACKGROUND: Müllerian inhibiting substance, produced constitutively by the prepubertal testes, promotes involution of the müllerian ducts during normal male sexual differentiation [9].
• Furthermore, measurement of serum mullerian inhibiting substance was more sensitive than serum testosterone measurement for the identification of children with abnormal testes (67 percent vs. 25 percent), whereas the specificity of the two tests was similar [9].
• Measurements of serum müllerian inhibiting substance in the evaluation of children with nonpalpable gonads [9].

Chemical compound and disease context of AMH

• We identified a new heterozygous SF1 gene mutation, C16X, in a 46, XY patient showing gonadal dysgenesis with normal adrenal function: low basal levels of AMH and testosterone (T), weak T response to hCG, hypoplastic testes with abundant seminiferous tubules but rare germ cells [10].
• We measured serum androgens, AMH and gonadotropins in 24 patients with sexual ambiguity and XY karyotype: 8 with gonadal dysgenesis (GD), 3 with 3beta-hydroxysteroid dehydrogenase deficiency (3betaHSD), 5 with androgen insensitivity syndrome (AIS), 4 with 5alpha-reductase 2 (SRD5A2) deficiency, and 4 were of unknown origin or idiopathic [11].
• PRIMARY OBJECTIVE: This study was performed to assess effects of amantadine (AMH), a dopaminergic agent and NMDA antagonist, on chronic traumatic brain injury (TBI) [12].
• Addition of MIS significantly decreased adenylyl cyclase activity in a steroid specific, pertussis toxin (PTX)-sensitive manner in oocyte membranes and microinjection of PTX into oocytes inhibited MIS-induced OM, suggesting the steroid activates a G(i) protein [13].
• MATERIALS AND METHODS: Serum levels of MIS, testosterone and androstenedione were measured in 29 boys with distal hypospadias (midshaft or less) and 21 normal boys undergoing circumcision [14].

Biological context of AMH

• For proper male sexual differentiation, anti-Müllerian hormone (AMH) must be tightly regulated during embryonic development to promote regression of the Müllerian duct [15].
• In this study, we demonstrate that the canonical SOX-binding site within the human AMH proximal promoter can bind the transcription factor SOX9, a Sertoli cell factor closely associated with Sertoli cell differentiation and AMH expression [15].
• AMH activates BMP-specific R-Smads and reporter genes [16].
• Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107 [2].
• MIS-treated cells accumulated in the G(1) phase of the cell cycle and subsequently underwent apoptosis [17].

Anatomical context of AMH

• To understand the hierarchies of these factors and their involvement in the developing testis, for the first time we show the expression and subcellular localization of these factors by immunohistochemistry in the early human testis during embryogenesis compared with AMH expression [18].
• Components of the AMH signaling pathway have been identified in gonads and gonadal cell lines [16].
• Anti-Müllerian hormone (AMH) is a member of the Transforming Growth Factor-beta (TGF-beta) family implicated in the regression of Müllerian ducts in male fetuses and in the development and function of gonads of both sexes [16].
• In birds, AMH is expressed both in the male and female fetal gonads, and, like in reptiles, its expression is not preceded by that of SOX9 [19].
• When the hypothalamic-pituitary axis is active and the negative effect of androgens and germ cells is absent, for example, in the fetal and neonatal periods or in disorders like androgen insensitivity, FSH upregulates AMH expression through a nonclassical cAMP-PKA pathway involving transcription factors AP2 and NFkappaB [19].

Associations of AMH with chemical compounds

• In the testis, AMH is highly expressed by Sertoli cells of the testis from early fetal life to puberty, when it is downregulated by the action of testosterone, acting through the androgen receptor, and meiotic spermatocytes, probably acting through TNFalpha [19].
• (AMH/MIS) was first suggested by Jost, more than Four decades before this gonadal glycoprotein was purified and its gene and promoter sequenced [20].
• Reduction of epidermal growth factor receptor phosphorylation by activated Mullerian inhibiting substance is vanadate-sensitive [21].
• No relationship was found between AMH and age, serum estradiol, inhibin B, and LH levels in both groups [22].
• After multiple regression only the 2- to 5-mm FN remained significantly related to AMH in PCOS whereas testosterone, androstenedione, and FSH were no longer [22].

Regulatory relationships of AMH

• The carboxy-terminal domain of recombinant human Mullerian inhibiting substance (MIS) inhibits cellular proliferation in vitro and decreases epidermal growth factor (EGF)-dependent phosphorylation of the EGF receptor [21].
• Recombinant human Mullerian inhibiting substance inhibits long-term growth of MIS type II receptor-directed transgenic mouse ovarian cancers in vivo [23].
• These observations suggest that MIS regulates androgen-induced gene expression and growth in prostate cancer cells through a NFkappaB-dependent but Smad1-independent mechanism [24].
• In both breast and prostate cancer cells, MIS activated NFkB DNA binding activity and induced IEX-1, an immediate early gene which regulates cell growth and apoptosis [25].
• The antibodies LN-4 (macrophages), 27 E 10 (early stage inflammation marker), AMH 152 (activated macrophages) and MIB 1 (proliferation marker) did not react with these cell populations [26].

Other interactions of AMH

• Our work thus identifies SOX9 as an interaction partner of SF-1 that could be involved in the Sertoli cell-specific expression of AMH during embryogenesis [15].
• Finally, normal cervical tissue expresses the MIS type II receptor in vivo, supporting the idea that MIS could be a targeted therapy for cervical cancer [2].
• Our results suggest that MIS is a natural substrate for PC5, thereby supporting a role for prohormone convertases in the activation of transforming growth factor beta-related hormones during development [27].
• High GATA-4 expression associates with aggressive behavior, whereas low anti-Müllerian hormone expression associates with growth potential of ovarian granulosa cell tumors [28].
• Furthermore, the over-expression of the exogenous SF-1 inhibited the activation of the MIS promoter with ER alpha [29].

Analytical, diagnostic and therapeutic context of AMH

• Serum MIS and the reproductive hormones were measured by standard immunoassays [30].
• In the present study, postnatal ovarian AMH and AMHRII messenger RNA (mRNA) expression was studied by in situ hybridization and ribonuclease protection [31].
• DNA was obtained from a 3-month-old patient with PMDS, in whom no serum anti-Müllerian hormone (AMH) could be detected by enzyme-linked immunosorbent assay [32].
• Therefore, we studied the relationship between AMH levels and ovarian response during ovarian stimulation for IVF [33].
• Serum AMH returns to normal infantile values 3-6 months after treatment [34].

References