Disease relevance of Amh

• One such hormone, Mullerian inhibiting substance (MIS), has been shown to inhibit DNA synthesis and steroidogenesis in primary Leydig cells and Leydig cell tumor lines [1].
• Furthermore, immunostaining for AMH was strongly increased after decapitation [2].
• The fall in MIS mRNA expression is delayed by hypothyroidism in vivo, indicating that T3 could regulate MIS mRNA [3].
• Bilateral anodal lesions performed with stainless steel electrodes placed either in the anterior medial (AMH) or lateral (ALH) hypothalamus, or in the ventromedial nucleus (VMH), induced in unrestrained rats the rapid development of arterial hypertension, tachycardia and death [4].

High impact information on Amh

• Regression of the fetal rat Müllerian duct in vitro was stimulated by sodium fluoride in the absence of Müllerian inhibiting substance [5].
• The action of Müllerian inhibiting substance was inhibited by sodium vanadate, adenosine 5'-triphosphate, and several related nucleotides in the presence of manganese ions [5].
• The MIS type II receptor (MISRII), which provides specificity for MIS, is also expressed in the adult testis, ovary, and uterus [6].
• Transcriptional regulation of the rat Müllerian inhibiting substance type II receptor in rodent Leydig cells [6].
• The MIS type II receptor (MISRII)-expressing cells are initially present in the coelomic epithelium of both male and female urogenital ridges, and then migrate into the mesenchyme surrounding the male Müllerian duct under the influence of MIS [7].

Biological context of Amh

• These data suggest that MIS inhibits regeneration of Leydig cells in EDS-treated rats by enhancing apoptotic cell death as well as by decreasing proliferative capacity [1].
• To further delineate the effects of MIS on Leydig cell proliferation and steroidogenesis, we employed the established ethylene dimethanesulphonate (EDS) model of Leydig cell regeneration [1].
• We report here the complete nucleotide sequence of the rat MIS gene [8].
• Rat MIS is encoded in five exons and is synthesized as a precursor of 553 amino acids, containing a 24-amino-acid leader [8].
• Mullerian inhibiting substance (MIS), a testicular glycoprotein also known as anti-Mullerian hormone, plays a key role in male sexual development by causing regression of the Mullerian duct, the anlagen of the uterus, the Fallopian tubes, and part of the vagina [8].

Anatomical context of Amh

• Müllerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Müllerian duct regression [7].
• The expression levels of both MIS mRNA and protein in the granulosa cells of small growing follicles in the ovary at P6 were higher in the EB-treated rats than in the controls [9].
• The rat gene should provide a good model for studying transcriptional regulation of MIS in the testis and ovary [8].
• Following EDS ablation of differentiated Leydig cells in young adult rats, recombinant MIS or vehicle was delivered by intratesticular injection for 4 days (Days 11-14 after EDS) [1].
• Modulation of endogenous GATA-4 activity reveals its dual contribution to Müllerian inhibiting substance gene transcription in Sertoli cells [10].

Associations of Amh with chemical compounds

• In the present study, we examined whether the expression of MIS and several of its related transcription factors is altered in the ovaries of rats treated with the synthetic estrogen, E2 benzoate (EB; 10 microg/0.02 ml), from postnatal day 1 (P1) to P5 [9].
• Increased expression of Müllerian-inhibiting substance correlates with inhibition of follicular growth in the developing ovary of rats treated with E2 benzoate [9].
• Although serum testosterone and luteinizing hormone (LH) were no different, intratesticular testosterone was higher on Day 35 in MIS-treated animals [1].
• Müllerian-inhibiting substance inhibits rat Leydig cell regeneration after ethylene dimethanesulphonate ablation [1].
• Thyroid hormone and follicle-stimulating hormone regulate Müllerian-inhibiting substance messenger ribonucleic acid expression in cultured neonatal rat Sertoli cells [3].

Regulatory relationships of Amh

• Mullerian inhibiting substance ontogeny and its modulation by follicle-stimulating hormone in the rat testes [11].

Other interactions of Amh

• These results suggest the role of MIS in the regulation of follicular growth and the possible involvement of steroidogenic factor 1 and/or ER-beta in this molecular cascade may contribute to postnatal ovarian development [9].
• Apoptotic interstitial cells were observed only in the MIS-treated testes, not in the vehicle-treated group on Day 15 [1].
• Activin-A action was specific in that treatment with transforming growth factor (TGF)-beta1, inhibin-A, or Müllerian-inhibiting substance (MIS)--all related peptides--failed to produce statistically significant alterations in the steady-state levels of IGFBP-4 and IGFBP-5 transcripts [12].
• Finally, orexin-A suppressed the expression of key Sertoli cell genes, such as Müllerian-inhibiting substance and stem cell factor, and inhibited DNA synthesis in specific stages of the seminiferous epithelium [13].
• Before transdifferentiating into Sertoli-like cells, follicular cells of oocyte-depleted follicles initiate the expression of anti-Mullerian hormone and inhibin alpha-subunit that are typically synthesized by granulosa cells from the onset of follicular growth [14].

Analytical, diagnostic and therapeutic context of Amh

• On Days 15 and 35 after EDS (1 and 21 days post-MIS injections), endocrine function was assessed and testes were collected for stereology, immunohistochemistry, and assessment of proliferation and steroidogenesis [1].
• In addition to the morphological masculinization, functional masculinization was obtained since the ovaries produced the anti-Müllerian hormone as shown by bioassay and immunohistochemical procedures [15].
• RT-PCR analysis showed that AMH reduced aromatase activity by decreasing the amount of aromatase messenger RNA [16].
• Testicular fragments of 17-day fetuses and 6-day-old pups showed an increase relative to controls in Müllerian inhibiting substance activity in a graded organ culture bioassay system [17].
• In an effort to clone the receptor for Mullerian inhibiting substance, a member of the transforming growth factor-beta superfamily, oligonucleotide primers designed from conserved regions of these receptors' kinase domains were used for PCR amplification of fetal rat urogenital ridge cDNA [18].

References