Comments on ‘‘Inhibition of estrogen actions in human gynecological malignancies: New aspects of endocrine therapy for endometrial cancer and ovarian cancer’’ Dear Prof. Huhtaniemi, Editor in Chief of Molecular and Cellular Endocrinology. We have read with great interest the recently published paper by Ito and co-workers (Ito et al., 2011) on the contribution of estro- gen metabolism to endometrial and ovarian cancers. The study thoroughly reviews clinical investigations and trials testing hor- mone treatments for these disorders and underscores the transla- tional potential of our current knowledge for future possible therapeutic applications. Given the potential impact of this study for the readers of ‘Molecular and Cellular Endocrinology’, we would like to draw the author’s and editor’s attention to the fact that, with respect to endo- metrial cancer, and specifically to the role of the 17b-hydroxyster- oid dehydrogenase type 1 (17b-HSD type 1), the proposed model (illustrated in Fig. 1B of the aforementioned paper) is not up to date. After reviewing selected publications (Casey et al., 1994; Ito et al., 2001; Utsunomiya et al., 2001), the authors conclude that 17b-HSD type 1 is not expressed in normal, hyperplastic or malig- nant endometrium. However, a number of other studies have been published that did report expression of 17b-HSD type 1 in endome- trial cells, in normal endometrium and in endometrial pathological conditions, including endometrial cancer. Smuc and co-workers (Smuc et al., 2006) reported that 17b-HSD type 1 mRNA could be detected in endometrial biopsies (normal and cancer) as well as in endometrial cancer Ishikawa cells (Ito and co-workers cite this publication in their review but they decided to disregard the 17b-HSD type 1 data shown in the same paper). In a later study, the same authors (Smuc and Rizner, 2009) have detected 17b-HSD type 1 expression in a larger group of endometrial cancer biopsies and controls and – in two additional studies – among endometriosis patients and controls (Smuc et al., 2007, 2009). Type 1 17b-HSD expression was reported independently by several other investigators in normal endometrium (Maentausta et al., 1991; Miettinen et al., 1996), in endometrial cancer (Lepine et al., 2010), in endometrial hyperplasia (Bacallao et al., 2008), in primary endometrial cells (Aghajanova et al., 2009), in endometri- osis (Zeitoun et al., 1998), in endometrial cancer cell lines (Fournier and Poirier, 2009; Laplante et al., 2009) and in transplanted human endometrial tissue (Fechner et al., 2007). In conclusion, we are aware that the expression of type 1 17b-HSD in endometrial cells is low compared to other tissues and it can be easily overlooked if not sensitive enough assays are used. However, although based on the available published litera- ture a clear role for this enzyme in endometrial cancer has yet to be established, its expression, in endometrium and endometrial pathologies including cancer cannot be neglected. Yours Sincerely, Andrea Romano Gerard A.J. Dunselman Johannes L.H. Evers Roy F.P.M. Kruitwagen GROW: School for Oncology and Developmental Biology, Dept. of Obstetrics and Gynaecology, Maastricht University Medical Centre, The Netherlands E-mail address: a.romano@maastrichtuniversity.nl (A. Romano) Available online 22 August 2011 References Aghajanova, L., Hamilton, A., Kwintkiewicz, J., Vo, K.C., Giudice, L.C., 2009. Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biol. Reprod. 80, 105–114. Bacallao, K., Leon, L., Gabler, F., Soto, E., Romero, C., Valladares, L., Vega, M., 2008. In situ estrogen metabolism in proliferative endometria from untreated women with polycystic ovarian syndrome with and without endometrial hyperplasia. J. Steroid Biochem. Mol. Biol. 110, 163–169. Casey, M.L., MacDonald, P.C., Andersson, S., 1994. 17 Beta-hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium. J. Clin. Invest. 94, 2135–2141. Fechner, S., Husen, B., Thole, H., Schmidt, M., Gashaw, I., Kimmig, R., Winterhager, E., Grummer, R., 2007. Expression and regulation of estrogen-converting enzymes in ectopic human endometrial tissue. Fertil. Steril. 88, 1029–1038. Fournier, M.A., Poirier, D., 2009. Estrogen formation in endometrial and cervix cancer cell lines: involvement of aromatase, steroid sulfatase and 17beta- hydroxysteroid dehydrogenases (types 1, 5, 7 and 12). Mol. Cell. Endocrinol. 301, 142–145. Ito, K., Suzuki, T., Moriya, T., Utsunomiya, H., Sugawara, A., Konno, R., Sato, S., Sasano, H., 2001. Retinoid receptors in the human endometrium and its disorders: a possible modulator of 17 beta-hydroxysteroid dehydrogenase. J. Clin. Endocrinol. Metab. 86, 2721–2727. Ito, K., Utsunomiya, H., Niikura, H., Yaegashi, N., Sasano, H., 2011. Inhibition of estrogen actions in human gynecological malignancies: New aspects of endocrine therapy for endometrial cancer and ovarian cancer. Mol Cell Endocrinol. 340, 161–167. Laplante, Y., Rancourt, C., Poirier, D., 2009. Relative involvement of three 17beta- hydroxysteroid dehydrogenases (types 1, 7 and 12) in the formation of estradiol in various breast cancer cell lines using selective inhibitors. Mol. Cell. Endocrinol. 301, 146–153. Lepine, J., Audet-Walsh, E., Gregoire, J., Tetu, B., Plante, M., Menard, V., Ayotte, P., Brisson, J., Caron, P., Villeneuve, L., Belanger, A., Guillemette, C., 2010. Circulating estrogens in endometrial cancer cases and their relationship with 0303-7207/$ - see front matter Ó 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2011.08.023 Molecular and Cellular Endocrinology 363 (2012) 131–132 Contents lists available at SciVerse ScienceDirect Molecular and Cellular Endocrinology journal homepage: www.elsevier.com/locate/mce