Endometriosis is a benign disease of women during reproductive age[
17]; nevertheless, it is well known that endometriosic cells display functional properties that are typical of neoplastic cells, such as anti-apoptotic, invasive and metastatic capacities[
18,
19]. In support to this observation, epidemiological studies have shown that there exists an increased risk of different types of malignancies, especially ovarian cancer and non-Hodgkin’s lymphoma in women with endometriosis[
20,
21]. Nevertheless, it has been reported an association between endometriosis, dysplastic nevi, melanoma, and breast cancer[
22,
23]. Finally, several histological and genetic studies have indicated that endometriosis may transform into cancer or that it could be considered a precursor of cancer[
24]. Recently, it has been demonstrated by Wang et al., that adult human endometrium has a functional AMH/AMHRII signal transduction system and that the activation of this system is able to negatively regulate cellular viability in cultured endometrial cells[
12]. Indeed, the exact biological role of AMH in adult females is unclear. The most well recognized function in adult is its involvement in recruitment and selection of initial primordial follicles[
25]. In fact, there exists a plethora of research articles on the use of AMH serum level as a sensitive marker to assess the ovarian reserve[
26]. However, consistently with the work by Wang et al.[
12], 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 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 and to induce apoptosis in endometriosis cells, both epithelial and stromal. Several experimental studies have revealed that AMH is strongly activated by cleavage[
34]. In fact, the C-terminal fragment contains the conserved TGFβ domain[
35] and the cleavage is necessary for efficient receptor binding[
36]. Consistent with these observation, it has been reported that the plasmin-digested AMH is more active in cultured human endometrial cell lines[
15]. 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[
15]. Several studies have suggested that endometriosis implants are able to produce estrogen
de novo from cholesterol[
37]. Therefore, endogenous steroidogenic genes in local estradiol biosynthesis in endometriosis 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 C
19 steroids to estrogens[
38], thus suggesting a possible biological explanation of the effects of this hormone on cell growth and apoptosis.