Mullerian Inhibiting Substance: Studies on its Mechanism of Action and Activity as an Anti-Tumor Agent

  • David T. MacLaughlin
  • James Epstein
  • Patricia K. Donahoe
Part of the Reproductive Biology book series (RBIO)


The urogenital ridge of the developing mammalian embryo is a complex structure in which the Wolffian and Mullerian ducts, each comprised of luminal epithelium surrounded by mesenchyme, develop side by side. As the maturing gonad begins to declare its genetic sex as either an ovary or testis, significant changes occur in the ducts contained within the urogenital ridge. If the gonad is an ovary the Wolffian duct, which develops into the epididymis, vas deferens, and seminal vesicles of the male, begins to atrophy while the Mullerian ducts expand. Conversely, testicular development coincides with the regression of the Mullerian ducts, the precursor of the ovarian coelomic epithelium, Fallopian tubes, uterus, cervix, and upper third of the vagina. As expected in this case, the Wolffian duct continues to enlarge.


Epidermal Growth Factor Receptor Epidermal Growth Factor Wolffian Duct Mullerian Duct Mullerian Inhibit Substance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Blanchard M. and Josso N. 1974. Source of anti-Mullerian hormone synthesized by the fetal testis: Mullerian inhibiting activity of fetal bovine Sertoli cells in tissue culture. Ped. Res. 8:968.CrossRefGoogle Scholar
  2. Brautigen D.L., Bornstein P. and Gallis B. 1981 Phosphotryrosyl-protein phosphate: specific inhibition by zinc ion. J. Biol. Chem. 256:6519.Google Scholar
  3. Budzik G.P., Donahoe P.K. and Hutson J.M. 1985. A possible purification of Mullerian Inhibiting Substance and a model for its mechanism of action. In: “Developmental mechanism: normal and abnormal”. (Lash, J.W. and Saxen, L. eds.), Alan R. Liss Inc., New York, p. 207.Google Scholar
  4. Budzik G.P., Hutson J.M., Ikawa H. and Donahoe P.K. 1982. The role of zinc in Mullerian duct regression. Endocrinology. 110:1521.PubMedCrossRefGoogle Scholar
  5. Carpenter G., King L. and Cohen S. 1979. Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. J. Biol. Chem. 254:4884.PubMedGoogle Scholar
  6. Cate R.L., Mattaliano R.J., Hession C., Tizard R., Farber N.M., Cheung A., Ninfa E.G., Frey A.Z., Gash D.J., Chow E.P., Fisher R.A., Bertonis J.M., Torres G., Wallner B.P., Ramachandran K.L., Ragin R.C., Manganaro T.F., MacLaughlin D.T., and Donahoe P.K. 1986. Isolation of the bovine and human genes for Mullerian Inhibiting Substance and expression of the human gene in animal cells. Cell 45:685.PubMedCrossRefGoogle Scholar
  7. Cigarroa F., Coughlin J.P., Donahoe P.K., White M.F., Uitvlugt N. and MacLaughlin D.T. 1989. Recombinant Mullerian Inhibiting Substance inhibits epidermal growth factor receptor tyrosine kinase. Growth Factors. In press.Google Scholar
  8. Cohen S., Chinkers M. and Ushero M. 1981. EGF-receptor protein kinase phosphorylates tyrosine and may be related to the transforming kinase of Rous sarcoma virus. Cold Spring Harbor Conf. Cell Prolif. 8:801.Google Scholar
  9. Coughlin J.P., Donahoe P.K., Budzik G.P. and MacLaughlin D.T. 1987. Mullerian Inhibiting Substance blocks autophosphorylation of the EGF receptor by inhibiting tyrosine kinase. Mol. Cell. Endocrinol. 49:75.PubMedCrossRefGoogle Scholar
  10. Donahoe P.K., Cate R.L., MacLaughlin D.T., Epstein J., Fuller A.F., Takahashi M., Coughlin J.P., Ninfa E.G., and Taylor L.A. 1987. Mullerian Inhibiting Substance: gene structure and mechanism of action of a fetal regressor. Recent Progm. Horm. Res. 43:431.Google Scholar
  11. Donahoe P.K., Fuller A.F., Scully R.E., Guy S.R., and Budzik G.P. 1981. Mullerian Inhibiting Substance inhibits growth of human ovarian cancer in nude mice. Ann. Surg. 194:472.PubMedCrossRefGoogle Scholar
  12. Donahoe P.K., Hutson J.M., Fallat M.E., Kamagata S. and Budzik G.P. 1984. Mechanism of action of Mullerian Inhibiting Substance. Ann. Rev. Physiol. 46:53.CrossRefGoogle Scholar
  13. Donahoe P.K., Swann D.A., Hayashi A. and Sullivan M.D. 1979. Mullerian duct regression in the embryo correlated with cytotoxic activity against human ovarian cancer. Science 205:913.PubMedCrossRefGoogle Scholar
  14. Fuller A.F., Budzik G.P., Krane I.M. and Donahoe P.K. 1984. Mullerian Inhibiting Substance inhibition of a human endometrial carcinoma cell line xenografted into nude mice. Gynecol. Oncol. 17:124.PubMedCrossRefGoogle Scholar
  15. Fuller A.F., Guy S., Budzik G.P. and Donahoe P.K. 1982. Mullerian Inhibiting Substance inhibits colony growth of a human ovarian cell line. J. Clin. Endocrinol. Metab. 54:1051.PubMedCrossRefGoogle Scholar
  16. Fuller A.F., Krane I.M., Budzik G.P. and Donahoe P.K. 1985. Mullerian Inhibiting Substance reduction of colony growth of human. Gynecol. Oncol. 22:135.PubMedCrossRefGoogle Scholar
  17. Hayashi M., Shima H., Trelstad R. and Donahoe P.K. 1984. Immunocyto-chemical localization of Mullerian Inhibiting Substance in rough endoplasmic reticulum and Golgi apparatus in Sertoli cells of the neonatal calf using a monoclonal antibody. J. Histochem. Cytochem. 32:649.PubMedCrossRefGoogle Scholar
  18. Hutson J.M. and Donahoe P.K. 1986. The hormonal control of testicular descent. Endocrine Rev. 7:270.CrossRefGoogle Scholar
  19. Hutson J.M., Donahoe P.K. and MacLaughlin D.T. 1985. Steroid modualtion of Mullerian duct regeneration in the chick embryo. Gen. Comp. Endocrinol. 57:88.PubMedCrossRefGoogle Scholar
  20. Hutson J. M., Fallat M.E., Kamagata S., Donahoe P.K. and Budzik G.P. 1984. Phosphorylation events during Mullerian duct regression. Science 223:586.PubMedCrossRefGoogle Scholar
  21. Ikawa H., Hutson J.M., Budzik G.P., MacLaughlin D.T. and Donahoe P.K. 1982. Steroid enhancement of Mullerian duct regression. J. Ped. Surg. 17:453.CrossRefGoogle Scholar
  22. Josso N., Picard J.Y. and Tran D. 1977. The anti-Mullerian hormone. Recent Progm. Horm. Res. 33:117.Google Scholar
  23. Jost A. 1946. Sur la differenciation sexuelle de l’embryon de lapin. Experiences de parabiose. C.R. Soc. Biol. 140:463.Google Scholar
  24. Jost A. 1946. Sur la differenciation sexuelle de l’embryon de lapin remarques au sujet des certaines operations chirurgical sur l’embryon. C.R. Soc. Biol. 140:461.Google Scholar
  25. Jost A. 1947. Sur les derives Mulleriens d’embryons de lapin des deux sexes castres a 21 jours. C.R. Soc. Biol. 141:135.Google Scholar
  26. Necklaws E., LaQuaglia M., MacLaughlin D.T., Hudson P., Mudgett-Hunter M. and Donahoe P.K. 1986. Detection of Mullerian Inhibiting Substance in biological samples by a solid phase sandwich radioimmunoassay. Endocrinology 2:791.CrossRefGoogle Scholar
  27. Pepinsky R.B., Sinclair L.K., Chow E.P., Mattaliano R.J., Manganaro T.F., Donahoe P.K. and Cate R.L. 1988. Proteolytic processing of Mullerian Inhibiting Substance produces a TGF-β like fragment. J. Biol. Chem. 263:18961.PubMedGoogle Scholar
  28. Picard J-Y., Benarous R., Guerrier D., Josso N., and Kahn A. 1986. Cloning and expression of cDNA for anti-Mullerian hormone. Biochemistry 83:5464.Google Scholar
  29. Picon R. 1969. Action du testicule feotal sur le development in vitro des canaux de Muller chez le rat. Arch. Anat. Morph. Exp. 58:1.Google Scholar
  30. Takahashi M., Hayashi M., Manganaro T.F., and Donahoe P.K. 1986a. The ontogeny of Mullerian Inhibiting Substance in granulosa cells of the bovine ovarian follicle. Biol. Reprod. 35:447.PubMedCrossRefGoogle Scholar
  31. Takahashi M., Koide S.S. and Donahoe P.K. 1986b. Mullerian Inhibiting Substance as oocyte meiosis inhibitor. Mol. Cell. Endocrinol. 47:225.PubMedCrossRefGoogle Scholar
  32. Ueno S., Manganaro T.F. and Donahoe P.K. 1988. Human recombinant Mullerian Inhibiting Substance inhibition of rat oocyte meiosis is reversed by epidermal growth in vitro. Encodrinol. 123:1652.CrossRefGoogle Scholar
  33. Vigier B., Picard J-Y., Tran D., Leageal L., and Josso N. 1984. Production of anti-Mullerian hormone: another homology between Sertoli and granulosa cells. Endocrinol. 114:1315.CrossRefGoogle Scholar
  34. Yamada T. 1974. The cellular biology of a newly established cell line of human ovarian adenocarcinoma in vitro. Keio J. Med. 23:53.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • David T. MacLaughlin
    • 1
  • James Epstein
    • 2
  • Patricia K. Donahoe
    • 2
  1. 1.Vincent Research LaboratoryMassachusetts General HospitalBostonUSA
  2. 2.Pediatric Surgical Research LaboratoryMassachusetts General HospitalBostonUSA

Personalised recommendations