help button home button Endocrine Society Endocrine Reviews
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Teixeira, J.
Right arrow Articles by Donahoe, P. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Teixeira, J.
Right arrow Articles by Donahoe, P. K.
Endocrine Reviews 22 (5): 657-674
Copyright © 2001 by The Endocrine Society

Müllerian Inhibiting Substance: An Instructive Developmental Hormone with Diagnostic and Possible Therapeutic Applications

Jose Teixeira, Shyamala Maheswaran and Patricia K. Donahoe

Pediatric Surgical Research Laboratories, Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114

Correspondence: Address all correspondence and requests for reprints to: Jose Teixeira, Pediatric Surgery/WRN1024, 32 Fruit Street, Boston, Massachusetts 02114. E-mail: teixeira{at}helix.mgh.harvard.edu

Dr. Alfred Jost pioneered the field of reproductive endocrinology with his seminal observation that two hormones produced by the testes are required for the male embryo to develop a normal internal reproductive tract. T induces the Wolffian ducts to differentiate into epididymides, vasa deferens, and seminal vesicles. Müllerian inhibiting substance (MIS) causes regression of the Müllerian ducts, which in its absence would normally develop into the Fallopian tubes, uterus, and upper vagina as is observed in female embryos. This review will summarize our current understanding of molecular mechanisms underlying the function of MIS both as a fetal gonadal hormone that causes Müllerian duct regression and as an adult hormone, the roles for which are currently being investigated, i.e., inhibition of steroidogenesis, germ cell development, and cancer. We will also address the regulation of MIS expression as one of the first genes expressed after the commitment of the bipotential gonads to differentiate into testes under the influence of SRY, the gene on the sex-determining region of the Y chromosome. We will discuss what is known regarding MIS signal transduction, which as with other members of the TGFß family of growth and differentiation factors, occurs through a heteromeric complex of single transmembrane serine/threonine kinase receptors to effect downstream signaling events, including Smad, nuclear factor-{kappa}B, ß-catenin, and p16 activation. Finally, we will assess the clinical relevance of studying MIS in patients with persistent Müllerian duct syndrome and our efforts to determine the therapeutic value of MIS for patients with ovarian and other MIS receptor-expressing cancers.




This article has been cited by other articles:


Home page
 Hum ReprodHome page
A.A. Sinisi, D. Esposito, L. Maione, M.C. Quinto, D. Visconti, A. De Bellis, A. Bellastella, G. Conzo, and G. Bellastella
Seminal anti-Mullerian hormone level is a marker of spermatogenic response during long-term gonadotropin therapy in male hypogonadotropic hypogonadism
Hum. Reprod., May 1, 2008; 23(5): 1029 - 1034.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
R. S. Viger, S. M. Guittot, M. Anttonen, D. B. Wilson, and M. Heikinheimo
Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease
Mol. Endocrinol., April 1, 2008; 22(4): 781 - 798.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. Renlund, R. Pieretti-Vanmarcke, F. H. O'Neill, L. Zhang, P. K. Donahoe, and J. Teixeira
c-Jun N-terminal Kinase Inhibitor II (SP600125) Activates Mullerian Inhibiting Substance Type II Receptor-Mediated Signal Transduction
Endocrinology, January 1, 2008; 149(1): 108 - 115.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
B. Kohler, A.-L. Delezoide, B. Boizet-Bonhoure, M. J McPhaul, C. Sultan, and S. Lumbroso
Coexpression of Wilms' tumor suppressor 1 (WT1) and androgen receptor (AR) in the genital tract of human male embryos and regulation of AR promoter activity by WT1
J. Mol. Endocrinol., May 1, 2007; 38(5): 547 - 554.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
X. Yin, S. Ouyang, W. Xu, X. Zhang, K. L. Fok, H. Y. Wong, J. Zhang, X. Qiu, S. Miao, H. C. Chan, et al.
YWK-II protein as a novel Go-coupled receptor for Mullerian inhibiting substance in cell survival
J. Cell Sci., May 1, 2007; 120(9): 1521 - 1528.
[Abstract] [Full Text] [PDF]

Home page
 Stem CellsHome page
P. P. Szotek, H. L. Chang, L. Zhang, F. Preffer, D. Dombkowski, P. K. Donahoe, and J. Teixeira
Adult Mouse Myometrial Label-Retaining Cells Divide in Response to Gonadotropin Stimulation
Stem Cells, May 1, 2007; 25(5): 1317 - 1325.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T. T. Tran, D. L. Segev, V. Gupta, H. Kawakubo, G. Yeo, P. K. Donahoe, and S. Maheswaran
Mullerian Inhibiting Substance Regulates Androgen-Induced Gene Expression and Growth in Prostate Cancer Cells through a Nuclear Factor-{kappa}B-Dependent Smad-Independent Mechanism
Mol. Endocrinol., October 1, 2006; 20(10): 2382 - 2391.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
T. Ebner, M. Sommergruber, M. Moser, O. Shebl, E. Schreier-Lechner, and G. Tews
Basal level of anti-Mullerian hormone is associated with oocyte quality in stimulated cycles
Hum. Reprod., August 1, 2006; 21(8): 2022 - 2026.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
Y. Zhan, A. Fujino, D. T. MacLaughlin, T. F. Manganaro, P. P. Szotek, N. A. Arango, J. Teixeira, and P. K. Donahoe
Mullerian inhibiting substance regulates its receptor/SMAD signaling and causes mesenchymal transition of the coelomic epithelial cells early in Mullerian duct regression
Development, June 15, 2006; 133(12): 2359 - 2369.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
R. Pieretti-Vanmarcke, P. K. Donahoe, P. Szotek, T. Manganaro, M. K. Lorenzen, J. Lorenzen, D. C. Connolly, E. F. Halpern, and D. T. MacLaughlin
Recombinant Human Mullerian Inhibiting Substance Inhibits Long-term Growth of MIS Type II Receptor-Directed Transgenic Mouse Ovarian Cancers In vivo
Clin. Cancer Res., March 1, 2006; 12(5): 1593 - 1598.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Anttonen, L. Unkila-Kallio, A. Leminen, R. Butzow, and M. Heikinheimo
High GATA-4 Expression Associates with Aggressive Behavior, whereas Low Anti-Mullerian Hormone Expression Associates with Growth Potential of Ovarian Granulosa Cell Tumors
J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6529 - 6535.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
P.-Y. Wang, K. Koishi, A. B. McGeachie, M. Kimber, D. T. MacLaughlin, P. K. Donahoe, and I. S. McLennan
Mullerian Inhibiting Substance acts as a motor neuron survival factor in vitro
PNAS, November 8, 2005; 102(45): 16421 - 16425.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. A. Rey, E. Codner, G. Iniguez, P. Bedecarras, R. Trigo, C. Okuma, S. Gottlieb, I. Bergada, S. M. Campo, and F. G. Cassorla
Low Risk of Impaired Testicular Sertoli and Leydig Cell Functions in Boys with Isolated Hypospadias
J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6035 - 6040.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
A. La Marca, S. Giulini, R. Orvieto, V. De Leo, and A. Volpe
Anti-Mullerian hormone concentrations in maternal serum during pregnancy
Hum. Reprod., June 1, 2005; 20(6): 1569 - 1572.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
V. Gupta, J. L. Carey, H. Kawakubo, A. Muzikansky, J. E. Green, P. K. Donahoe, D. T. MacLaughlin, and S. Maheswaran
Mullerian inhibiting substance suppresses tumor growth in the C3(1)T antigen transgenic mouse mammary carcinoma model
PNAS, March 1, 2005; 102(9): 3219 - 3224.
[Abstract] [Full Text] [PDF]

Home page
 J AndrolHome page
R. S. Viger, H. Taniguchi, N. M. Robert, and J. J. Tremblay
The 25th Volume: Role of the GATA Family of Transcription Factors in Andrology
J Androl, July 1, 2004; 25(4): 441 - 452.
[Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. J. Jorgez, M. Klysik, S. P. Jamin, R. R. Behringer, and M. M. Matzuk
Granulosa Cell-Specific Inactivation of Follistatin Causes Female Fertility Defects
Mol. Endocrinol., April 1, 2004; 18(4): 953 - 967.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. P. Houk, E. J. Pearson, N. Martinelle, P. K. Donahoe, and J. Teixeira
Feedback Inhibition of Steroidogenic Acute Regulatory Protein Expression in Vitro and in Vivo by Androgens
Endocrinology, March 1, 2004; 145(3): 1269 - 1275.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A. Salva, M. P. Hardy, X.-f. Wu, C. M. Sottas, D. T. MacLaughlin, P. K. Donahoe, and M. M. Lee
Mullerian-Inhibiting Substance Inhibits Rat Leydig Cell Regeneration after Ethylene Dimethanesulphonate Ablation
Biol Reprod, March 1, 2004; 70(3): 600 - 607.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
D. T. MacLaughlin and P. K. Donahoe
Sex Determination and Differentiation
N. Engl. J. Med., January 22, 2004; 350(4): 367 - 378.
[Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y. Hoshiya, V. Gupta, H. Kawakubo, E. Brachtel, J. L. Carey, L. Sasur, A. Scott, P. K. Donahoe, and S. Maheswaran
Mullerian Inhibiting Substance Promotes Interferon {gamma}-induced Gene Expression and Apoptosis in Breast Cancer Cells
J. Biol. Chem., December 19, 2003; 278(51): 51703 - 51712.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. J. Tremblay and R. S. Viger
A Mutated Form of Steroidogenic Factor 1 (SF-1 G35E) That Causes Sex Reversal in Humans Fails to Synergize with Transcription Factor GATA-4
J. Biol. Chem., October 24, 2003; 278(43): 42637 - 42642.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
C. Y. Hong, J. H. Park, K. H. Seo, J.-M. Kim, S. Y. Im, J. W. Lee, H.-S. Choi, and K. Lee
Expression of MIS in the Testis Is Downregulated by Tumor Necrosis Factor Alpha through the Negative Regulation of SF-1 Transactivation by NF-{kappa}B
Mol. Cell. Biol., September 1, 2003; 23(17): 6000 - 6012.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
G. Y. Bedecarrats, F. H. O'Neill, E. R. Norwitz, U. B. Kaiser, and J. Teixeira
Regulation of gonadotropin gene expression by Mullerian inhibiting substance
PNAS, August 5, 2003; 100(16): 9348 - 9353.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. Lukas-Croisier, C. Lasala, J. Nicaud, P. Bedecarras, T. R. Kumar, M. Dutertre, M. M. Matzuk, J.-Y. Picard, N. Josso, and R. Rey
Follicle-Stimulating Hormone Increases Testicular Anti-Mullerian Hormone (AMH) Production through Sertoli Cell Proliferation and a Nonclassical Cyclic Adenosine 5'-Monophosphate-Mediated Activation of the AMH Gene
Mol. Endocrinol., April 1, 2003; 17(4): 550 - 561.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
D. C. Connolly, R. Bao, A. Y. Nikitin, K. C. Stephens, T. W. Poole, X. Hua, S. S. Harris, B. C. Vanderhyden, and T. C. Hamilton
Female Mice Chimeric for Expression of the Simian Virus 40 TAg under Control of the MISIIR Promoter Develop Epithelial Ovarian Cancer
Cancer Res., March 15, 2003; 63(6): 1389 - 1397.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Misra, D. T. MacLaughlin, P. K. Donahoe, and M. M. Lee
The Role of Mullerian Inhibiting Substance in the Evaluation of Phenotypic Female Patients with Mild Degrees of Virilization
J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 787 - 792.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R. Fanchin, L. M. Schonauer, C. Righini, N. Frydman, R. Frydman, and J. Taieb
Serum anti-Mullerian hormone dynamics during controlled ovarian hyperstimulation
Hum. Reprod., February 1, 2003; 18(2): 328 - 332.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
H. Chang, C. W. Brown, and M. M. Matzuk
Genetic Analysis of the Mammalian Transforming Growth Factor-{beta} Superfamily
Endocr. Rev., December 1, 2002; 23(6): 787 - 823.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
Y. Kubota, C. Temelcos, R.A.D. Bathgate, K.J. Smith, D. Scott, C. Zhao, and J.M. Hutson
The role of insulin 3, testosterone, Mullerian inhibiting substance and relaxin in rat gubernacular growth
Mol. Hum. Reprod., October 1, 2002; 8(10): 900 - 905.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
V. M. Laurich, A. M. Trbovich, F. H. O'Neill, C. P. Houk, P. M. Sluss, A. H. Payne, P. K. Donahoe, and J. Teixeira
Mullerian Inhibiting Substance Blocks the Protein Kinase A-Induced Expression of Cytochrome P450 17{alpha}-Hydroxylase/C17-20 Lyase mRNA in a Mouse Leydig Cell Line Independent of cAMP Responsive Element Binding Protein Phosphorylation
Endocrinology, September 1, 2002; 143(9): 3351 - 3360.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Misra, D. T. MacLaughlin, P. K. Donahoe, and M. M. Lee
Measurement of Mullerian Inhibiting Substance Facilitates Management of Boys with Microphallus and Cryptorchidism
J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3598 - 3602.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. E. Stephen, L. A. Pearsall, B. P. Christian, P. K. Donahoe, J. P. Vacanti, and D. T. MacLaughlin
Highly Purified Mullerian Inhibiting Substance Inhibits Human Ovarian Cancer in Vivo
Clin. Cancer Res., August 1, 2002; 8(8): 2640 - 2646.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society