, several papers have shown a part for AMH as a regulator of cell growth in cells and tissues of Mullerian origins, such as endometrial, ovarian, cervical and breast tissues and find more a role for AMH as potential therapeutic factor in tumors originating from these tissues has been proposed [27–31]. Recently, two independent research groups have demonstrated
that the AMH system is active also in endometriosic cells in vitro and that it acts as a negative regulator of cell cycle and cell viability [32, 33]. In this study we have shown that AMH protein is clearly expressed in endometriosis glands in humans; that it is also expressed together with its receptor AMH RII in our in vitro model of endometriosis; and that it is able to inhibit cell proliferation BIX 1294 purchase and to induce apoptosis in endometriosis cells, both epithelial and stromal. Several experimental studies have revealed that AMH is strongly activated by cleavage . In fact, the C-terminal fragment contains the conserved TGFβ domain  and the cleavage is necessary for efficient receptor binding . this website Consistent with these observation, it has been reported that the plasmin-digested AMH is more active in cultured
human endometrial cell lines . In our experimental setting, we have been able to demonstrate that cleaved AMH is effective in inhibiting cell proliferation in endometriosis cells. Moreover, this cleaved form of AMH is able to inhibit most of the CYP19 activity in endometriosis cells, as it has been already shown for cultured granulosa lutein cells . Several studies have suggested that endometriosis implants are able to produce estrogen de novo from cholesterol . Therefore, endogenous steroidogenic genes in local estradiol biosynthesis in endometriosis Oxaprozin are crucial for the survival of these implants. Based on this rationale, it has been recently proposed the use of aromatase inhibitors
as a novel treatment of endometriosis. Our experimental data demonstrate, indeed, that AMH treatment is able to inhibit CYP19 activity, that is the key enzyme in humans for the conversion of C19 steroids to estrogens , thus suggesting a possible biological explanation of the effects of this hormone on cell growth and apoptosis. Conclusions The clinical and therapeutic implications of this observation are straightforward. In fact, all current endometriosis treatments, including surgical and medical strategies, have high recurrence rates of up to 45% . The data produced suggest a possible use of AMH as therapeutic agents in endometriosis. Additional functional studies both in vitro and in vivo are necessary in order to define applicable therapeutic modalities. References 1. Bulun SE: Endometriosis. New Engl J Med 2009, 360:268–279.PubMedCrossRef 2. Cramer DW, Missmer SA: The epidemiology of endometriosis. Ann N Y Acad Sci 2002, 955:11–22.PubMedCrossRef 3. Baldi A, Campioni M, Signorile PG: Endometriosis: pathogenesis, diagnosis, therapy and association with cancer.