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Gene Review

Amh  -  anti-Mullerian hormone

Mus musculus

Synonyms: AMH, Anti-Muellerian hormone, MIS, Muellerian-inhibiting factor, Muellerian-inhibiting substance, ...
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Disease relevance of Amh

  • Mutations in mullerian inhibiting substance (MIS) or MISRII cause male sexual abnormalities, persistent mullerian duct syndrome, and pseudohermaphroditism [1].
  • Collectively, these results suggest that in the absence of MIS, Leydig cells remain less differentiated, causing an altered intratesticular androgen milieu that may contribute to the infertility of MIS-KO mice [2].
  • MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered [2].
  • To extend the use of MIS to treat breast cancer, it is essential to test the responsiveness of mammary tumor growth to MIS in vivo [3].
  • For example, breast and prostate cancer cell lines use a MIS-mediated NFkappaB pathway leading to G1 arrest and apoptosis [4].

High impact information on Amh

  • These results identify Bmpr1a as a type I receptor for Amh-induced regression of Müllerian ducts [5].
  • Mutations in AMH or AMHR2 in humans and mice disrupt signaling, producing male pseudohermaphrodites that possess oviducts and uteri [5].
  • Male mice homozygous for the mutant SF1-binding site correctly initiated Mis transcription in fetal testes, although at significantly reduced levels [6].
  • Surprisingly, sufficient MIS was produced to eliminate the MUllerian ducts [6].
  • Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development [6].

Chemical compound and disease context of Amh


Biological context of Amh


Anatomical context of Amh

  • During an investigation of the regulatory potential of a region 5' of the mouse anti-müllerian hormone (Amh) gene, we identified a region of homology with the known cDNA sequence of a human spliceosome gene (SAP62) [14].
  • Expression of Sox8 begins just prior to that of Amh at 12 days post coitum (dpc) in mouse testes and continues beyond 16 dpc in Sertoli cells [10].
  • Recently, co-culture of isolated oocytes and granulosa cells has demonstrated that Amh expression is up-regulated in the presence of oocytes and, at preantral stages, this effect is dependent upon close contact [15].
  • However, our studies involving the red-eared slider turtle indicate that Sox8 is expressed at similar levels in males and females throughout the sex-determining period, suggesting that Sox8 is neither a transcriptional regulator for Amh, nor responsible for sex determination or gonad differentiation in that species [16].
  • Using LbetaT2 cells, a murine gonadotrope-derived cell line, we have evaluated the effects of MIS on the expression of the gonadotropin genes [11].

Associations of Amh with chemical compounds


Physical interactions of Amh

  • Furthermore DNA-protein interaction in in vitro studies showed first that GATA-1 binds with various affinities on sites found in the AMH promoter and second that the proximity of the two strongest affinity sites leads to a synergistic binding effect [20].

Regulatory relationships of Amh


Other interactions of Amh

  • These results allowed us to define a transitory 4-5-day period, starting from 3 dpp when both proteins are heterogeneously expressed in Sertoli cells and showed that the appearance of GATA-1 is associated with the decrease of AMH expression in these cells [20].
  • Analysis of the role of Amh and Fra1 in the Sry regulatory pathway [24].
  • Deficiency of MIS or of the MIS type II receptor, MISRII, results in abnormal reproductive development in the male due to the maintenance of the duct [17].
  • ALK6 has been shown to function as an MIS type I receptor [17].
  • The reporter construct analysis, pattern of expression of the receptors, and analysis of ALK6-deficient animals suggest that ALK2 is the MIS type I receptor involved in Müllerian duct regression [17].

Analytical, diagnostic and therapeutic context of Amh


  1. Synergistic cooperation between the beta-catenin signaling pathway and steroidogenic factor 1 in the activation of the Mullerian inhibiting substance type II receptor. Hossain, A., Saunders, G.F. J. Biol. Chem. (2003) [Pubmed]
  2. Pubertal and adult Leydig cell function in Mullerian inhibiting substance-deficient mice. Wu, X., Arumugam, R., Baker, S.P., Lee, M.M. Endocrinology (2005) [Pubmed]
  3. Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model. Gupta, V., Carey, J.L., Kawakubo, H., Muzikansky, A., Green, J.E., Donahoe, P.K., MacLaughlin, D.T., Maheswaran, S. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  4. Enhanced purification and production of Müllerian inhibiting substance for therapeutic applications. Donahoe, P.K., Clarke, T., Teixeira, J., Maheswaran, S., MacLaughlin, D.T. Mol. Cell. Endocrinol. (2003) [Pubmed]
  5. Requirement of Bmpr1a for Müllerian duct regression during male sexual development. Jamin, S.P., Arango, N.A., Mishina, Y., Hanks, M.C., Behringer, R.R. Nat. Genet. (2002) [Pubmed]
  6. Targeted mutagenesis of the endogenous mouse Mis gene promoter: in vivo definition of genetic pathways of vertebrate sexual development. Arango, N.A., Lovell-Badge, R., Behringer, R.R. Cell (1999) [Pubmed]
  7. Receptors for anti-müllerian hormone on Leydig cells are responsible for its effects on steroidogenesis and cell differentiation. Racine, C., Rey, R., Forest, M.G., Louis, F., Ferré, A., Huhtaniemi, I., Josso, N., di Clemente, N. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  8. Hormonal factors in carcinogenesis of the prostate and testis in humans and in animal models. Bosland, M.C. Prog. Clin. Biol. Res. (1996) [Pubmed]
  9. Highly purified müllerian inhibiting substance inhibits human ovarian cancer in vivo. Stephen, A.E., Pearsall, L.A., Christian, B.P., Donahoe, P.K., Vacanti, J.P., MacLaughlin, D.T. Clin. Cancer Res. (2002) [Pubmed]
  10. SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro. Schepers, G., Wilson, M., Wilhelm, D., Koopman, P. J. Biol. Chem. (2003) [Pubmed]
  11. Regulation of gonadotropin gene expression by Mullerian inhibiting substance. Bédécarrats, G.Y., O'Neill, F.H., Norwitz, E.R., Kaiser, U.B., Teixeira, J. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  12. Mapping anti-müllerian hormone (Amh) and related sequences in the mouse: identification of a new region of homology between MMU10 and HSA19p. King, T.R., Lee, B.K., Behringer, R.R., Eicher, E.M. Genomics (1991) [Pubmed]
  13. Hormonal and cellular regulation of Sertoli cell anti-Müllerian hormone production in the postnatal mouse. Al-Attar, L., Noël, K., Dutertre, M., Belville, C., Forest, M.G., Burgoyne, P.S., Josso, N., Rey, R. J. Clin. Invest. (1997) [Pubmed]
  14. The genes for a spliceosome protein (SAP62) and the anti-Müllerian hormone (AMH) are contiguous. Dresser, D.W., Hacker, A., Lovell-Badge, R., Guerrier, D. Hum. Mol. Genet. (1995) [Pubmed]
  15. Expression of Sox8, Sf1, Gata4, Wt1, Dax1, and Fog2 in the mouse ovarian follicle: implications for the regulation of Amh expression. Salmon, N.A., Handyside, A.H., Joyce, I.M. Mol. Reprod. Dev. (2005) [Pubmed]
  16. Origin and possible roles of the Sox8 transcription factor gene during sexual development. Takada, S., Koopman, P. Cytogenet. Genome Res. (2003) [Pubmed]
  17. Müllerian inhibiting substance signaling uses a bone morphogenetic protein (BMP)-like pathway mediated by ALK2 and induces SMAD6 expression. Clarke, T.R., Hoshiya, Y., Yi, S.E., Liu, X., Lyons, K.M., Donahoe, P.K. Mol. Endocrinol. (2001) [Pubmed]
  18. Pod-1/Capsulin shows a sex- and stage-dependent expression pattern in the mouse gonad development and represses expression of Ad4BP/SF-1. Tamura, M., Kanno, Y., Chuma, S., Saito, T., Nakatsuji, N. Mech. Dev. (2001) [Pubmed]
  19. Directed expression of an oncogene to Sertoli cells in transgenic mice using mullerian inhibiting substance regulatory sequences. Peschon, J.J., Behringer, R.R., Cate, R.L., Harwood, K.A., Idzerda, R.L., Brinster, R.L., Palmiter, R.D. Mol. Endocrinol. (1992) [Pubmed]
  20. GATA-1 is a potential repressor of anti-Müllerian hormone expression during the establishment of puberty in the mouse. Beau, C., Rauch, M., Joulin, V., Jégou, B., Guerrier, D. Mol. Reprod. Dev. (2000) [Pubmed]
  21. Temperature-dependent sex determination in the American alligator: AMH precedes SOX9 expression. Western, P.S., Harry, J.L., Graves, J.A., Sinclair, A.H. Dev. Dyn. (1999) [Pubmed]
  22. Feedback inhibition of steroidogenic acute regulatory protein expression in vitro and in vivo by androgens. Houk, C.P., Pearson, E.J., Martinelle, N., Donahoe, P.K., Teixeira, J. Endocrinology (2004) [Pubmed]
  23. The LIM-only coactivator FHL2 modulates WT1 transcriptional activity during gonadal differentiation. Du, X., Hublitz, P., Günther, T., Wilhelm, D., Englert, C., Schüle, R. Biochim. Biophys. Acta (2002) [Pubmed]
  24. Analysis of the role of Amh and Fra1 in the Sry regulatory pathway. Jeske, Y.W., Mishina, Y., Cohen, D.R., Behringer, R.R., Koopman, P. Mol. Reprod. Dev. (1996) [Pubmed]
  25. Sox8 is expressed at similar levels in gonads of both sexes during the sex determining period in turtles. Takada, S., DiNapoli, L., Capel, B., Koopman, P. Dev. Dyn. (2004) [Pubmed]
  26. Involvement of a matrix metalloproteinase in MIS-induced cell death during urogenital development. Roberts, L.M., Visser, J.A., Ingraham, H.A. Development (2002) [Pubmed]
  27. The müllerian inhibitor and mammalian sexual development. Behringer, R.R. Philos. Trans. R. Soc. Lond., B, Biol. Sci. (1995) [Pubmed]
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