Müllerian inhibiting substance (MIS), also called anti-Müllerian
hormone (AMH), is a member of the
transforming growth factor-β super-family of growth and differentiation response modifiers. It is produced in immature Sertoli cells in male embryos and binds to MIS/AMH receptors in primordial Müllerian ducts to cause regression of female reproductive structures that are the precursors to the fallopian tubes, the surface epithelium of the ovaries, the uterus, the cervix, and the upper third of the vagina. Because most gynecologic
tumors originate from Müllerian duct-derived tissues, and since MIS/AMH causes regression of the Müllerian duct in male embryos, it is expected to inhibit the growth of gynecologic
tumors. Purified recombinant human MIS/AMH causes growth inhibition of
epithelial ovarian cancer cells and cell lines in vitro and in vitro via
MIS receptor-mediated mechanism. Furthermore, several lines of evidence suggest that MIS/AMH inhibits proliferation in tissues and cell lines of other MIS/
AMH receptor-expressing gynecologic
tumors such as cervical, endometrial, breast, and in
endometriosis as well. These findings indicate that bioactive MIS/AMH
recombinant protein should be tested in patients against
tumors expressing the MIS/
AMH receptor complex, perhaps beginning with
ovarian cancer because it has the worst prognosis. The molecular tools to identify MIS/
AMH receptor expressing ovarian and other
cancers are in place, thus, it is possible to select patients for treatment. An MIS/AMH ELISA exists to follow administered doses of MIS/AMH, as well. Clinical trials await the production of sufficient supplies of qualified recombinant human MIS/AMH for this purpose.