Disease relevance of AMH

• The monoclonal antibody purified from ascites fluid abolished anti-Müllerian activity of partially purified AMH, whether or not the immune complex was removed from solution by a second, antimouse immunoglobulin antibody [1].
• It is suggested that the similarity between the immunogenic characteristics of bovine, ovine and caprine AMH is in some way related to the fact that AMH in these species is disseminated in the blood stream and may produce freemartinism [2].
• A significant cytotoxicity index was obtained when human ovarian cancer cells in a microcytotoxicity assay were exposed during the S (DNA-synthesizing) phase of the cell cycle to purified fractions of testis exhibiting high Müllerian inhibiting substance bioactivity [3].
• Forty-three primary human tumor explants were also examined in human tumor colony forming assays, gel-supported primary culture assays, and subrenal capsule assays. rHu-MIS significantly inhibited the growth of five of these tumors including four ovarian and one small cell lung cancer explant [4].
• Anti-Müllerian hormone is not cytotoxic to human endometrial cancer in tissue culture [5].

High impact information on AMH

• Animal cells transfected with the human gene secrete biologically active MIS, which causes regression of the rat Müllerian duct in vitro [6].
• Mullerian inhibiting substance (MIS), a large glycoprotein secreted by the fetal and neonatal testis, is responsible for regression of the Mullerian ducts in the male embryo [7].
• A high yield of 60% recovered activity was achieved in the absence of exogenous carrier protein by stabilizing MIS with 2-mercaptoethanol, EDTA, and Nonidet-P40 and eliminating losses in the handling and concentration of MIS fractions [7].
• Electrophoresis of this fraction on polyacrylamide-SDS gels showed an identical band pattern after staining with either Coomassie blue or periodic acid-Schiff reagent, further indicating that MIS is a glycoprotein [8].
• AMH dramatically decreases the conversion rate of testosterone to estradiol and also decreases total aromatase activity, as measured by the tritiated water technique [9].

Chemical compound and disease context of AMH

• Whereas no effect was detected in the younger gonads, some structural changes were observed in bovine and 21-day-old rat ovaries when cultured for 5 days with Daudi and male teratoma supernatants, but there was no synthesis of testosterone or MIS [10].

Biological context of AMH

• Taken together, our results suggest that AMH plays a pivotal role in both morphological and endocrine gonadal sex differentiation [9].
• Hybridomas were screened for specific antibody production by double antibody precipitation of labeled AMH, which was obtained by incubating fetal calf testes in the presence of tritiated fucose and submitting the medium to the standard procedure of purification [1].
• A break or fusion between AMH and CSF2 in an ancestral chromosome is suggested to account for the current arrangement of these homologous segments in the human and bovine genomes [11].
• This may help to elucidate whether persistence of Müllerian ducts results from lack of testicular production of AMH or from peripheral resistance of the Müllerian primordia to the hormone [12].
• In contrast, in fetal rat ovaries, AMH did not trigger the testosterone production which occurs in freemartin gonads at an early stage of the gestation [13].

Anatomical context of AMH

• These data strongly suggest that AMH is the testicular factor responsible for triggering the morphological abnormalities of freemartin gonads [14].
• In cultures initiated at 14 days p.c. and maintained 3 to 10 days, AMH consistently induced a characteristic 'freemartin effect', namely reduction of gonadal volume, germ cell depletion and differentiation, in the gonadal blastema, of epithelial cells with large clear cytoplasm linked by interdigitations, resembling rat fetal Sertoli cells [14].
• Booster injections were given at Day 8 of pregnancy to ensure a high titer of anti-AMH antibodies at the time the rabbit fetal testis begins to produce AMH [15].
• These findings indicate that adult mammalian granulosa cells are capable of producing immunoreactive and bioactive AMH at a rate apparently similar to that already demonstrated for mature Sertoli cells and add yet another item to the homologies reported between male and female somatic gonadal cells [16].
• In spite of the extremely low concentration of AMH in the preparation used for immunization, three hybridomas gave positive results in the screening assay [1].

Associations of AMH with chemical compounds

• We have isolated the bovine and human genes for Müllerian inhibiting substance (MIS), a testicular glycoprotein that causes regression of the Müllerian duct during development of the male embryo [6].
• Ovine fetal ovaries exposed to AMH release testosterone instead of estradiol, an endocrine sex reversal due to suppression of aromatase activity [9].
• Under the same in vitro conditions, AMH treatment did not affect cyclic AMP-stimulated fetal rat testicular aromatase activity [17].
• Although the majority of the resulting hybridomas resembled those obtained previously insofar as they recognized only bovine, ovine and caprine AMH, four others, all immunoglobulin Ms, were directed against an epitope shared with AMH of other species, namely rabbit, pig and cat [2].
• Theophylline at 1.0 mM inhibited the action of the MIS fraction [18].

Other interactions of AMH

• Bovine anti-Müllerian hormone and osteonectin loci were fully concordant with each other in 96 hybrid somatic cell lines, but were not concordant with any other bovine syntenic group described to date [19].
• Immunocytochemical localization of Mullerian inhibiting substance in the rough endoplasmic reticulum and Golgi apparatus in Sertoli cells of the neonatal calf testis using a monoclonal antibody [20].

Analytical, diagnostic and therapeutic context of AMH

• Study of the ontogeny of the response of cyclic AMP-stimulated aromatase activity of rat fetal ovaries to AMH has allowed us to develop a quantitative bioassay for the hormone [17].
• The molecular weight of labelled AMH was 215,000 when determined by gel filtration and 124,000 when determined by density gradient sedimentation [21].
• By SDS-PAGE the molecular weight of labelled AMH was 123,000 and dissociation into a 72,000 subunit was demonstrated under conditions which reduce disulfide bonds [21].
• AMH obtained by this procedure has been studied using Coomassie blue and immunoblotting, and compared with fucose-labelled AMH, which is recognized by the same monoclonal antibodies as the carrier of the anti-Müllerian biological activity [22].
• Enhanced purification of Mullerian inhibiting substance by lectin affinity chromatography [8].

References