This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ito, K. Articles by Sasano, H. Search for Related Content PubMed PubMed Citation Articles by Ito, K. Articles by Sasano, H.

Retinoid Receptors in the Human Endometrium and Its Disorders: A Possible Modulator of 17ß-Hydroxysteroid Dehydrogenase¹

Departments of Obstetrics and Gynecology (K.I., H.U., R.K., S.S.), Pathology (T.S., T.M., H.S.), and Medicine II (A.S.), Tohoku University School of Medicine, Sendai 980-8557, Japan

Address all correspondence and requests for reprints to: Kiyoshi Ito, M.D., Department of Obstetrics and Gynecology, Tohoku University School of Medicine, 1-1 Seiryo-Machi, Aoba-ku, Sendai 980-8557, Japan. E-mail: kito{at}ob-gy.med.tohoku.ac.jp

Abstract

Retinoids have recently been proposed to modulate estrogenic actions in various sex steroid-dependent neoplasms, but little has been studied in human endometrial disorders. Therefore, in this study, we first examined the immunolocalization of retinoic acid receptor , ß, and , and retinoid X receptor (RXR) , ß, and in 20 normal cycling human endometria, 34 endometrial hyperplasia, and 46 endometrioid endometrial adenocarcinomas. We then correlated these findings with other clinicopathological parameters, especially in the correlation between retinoid receptor subtypes and the status of steroid hormone receptors, 17ß-hydroxysteroid dehydrogenase (17ß-HSD) and aromatase. We also then examined the effects of retinoic acid on the expression of 17ß-HSD type 2 in cell lines derived from endometrial carcinoma using Northern blotting analysis to examine the possible roles of retinoids in in situ endometrial estrogen metabolism. Among these six retinoid receptors examined, RXR immunoreactivity was exclusively detected in the epithelial cells of the secretory phase endometrium but not of the proliferative phase, which was well correlated with 17ß-HSD type 2 immunolocalization. However, in endometrial hyperplasia, RXR was not correlated with 17ß-HSD type 2. In endometrioid endometrial adenocarcinoma, there was a statistically significant correlation between 17ß-HSD type 2 immunoreactivity and RXR labeling index (LI) (P < 0.001) and between RXR LI and progesterone receptor LI (r = 0.501, P = 0.003).

A significant inverse correlation was also detected between RXR LI and patient age (r = 0.449, P = 0.015). No statistically significant correlation was obtained between LIs of receptors and other clinicopathological parameters including the status of intratumoral aromatase examined by immunohistochemistry. In the endometrial carcinoma cell line, RL95–2, retinoic acid markedly increased the level of 17ß-HSD type 2 messenger RNA in a time- and dose-dependent manner. These results all suggest that retinoic acids may be involved in modulation of in situ estrogen metabolism in both normal and neoplastic human endometrium possibly through RXR by stimulating the expression of 17ß-HSD type 2.

This article has been cited by other articles:

				Y.-H. Cheng, P. Yin, Q. Xue, B. Yilmaz, M. I. Dawson, and S. E. Bulun Retinoic Acid (RA) Regulates 17{beta}-Hydroxysteroid Dehydrogenase Type 2 Expression in Endometrium: Interaction of RA Receptors with Specificity Protein (SP) 1/SP3 for Estradiol Metabolism J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1915 - 1923. [Abstract] [Full Text] [PDF]

				P. Rantakari, L. Strauss, R. Kiviranta, H. Lagerbohm, J. Paviala, I. Holopainen, S. Vainio, P. Pakarinen, and M. Poutanen Placenta Defects and Embryonic Lethality Resulting from Disruption of Mouse Hydroxysteroid (17-{beta}) Dehydrogenase 2 Gene Mol. Endocrinol., March 1, 2008; 22(3): 665 - 675. [Abstract] [Full Text] [PDF]

				E. J Su, Y.-H. Cheng, R. T Chatterton, Z.-H. Lin, P. Yin, S. Reierstad, J. Innes, and S. E Bulun Regulation of 17-Beta Hydroxysteroid Dehydrogenase Type 2 in Human Placental Endothelial Cells Biol Reprod, September 1, 2007; 77(3): 517 - 525. [Abstract] [Full Text] [PDF]

				Y.-H. Cheng, A. Imir, T. Suzuki, V. Fenkci, B. Yilmaz, H. Sasano, and S. E. Bulun SP1 and SP3 Mediate Progesterone-Dependent Induction of the 17beta Hydroxysteroid Dehydrogenase Type 2 Gene in Human Endometrium Biol Reprod, October 1, 2006; 75(4): 605 - 614. [Abstract] [Full Text] [PDF]

				K. Ota, K. Ito, T. Suzuki, S. Saito, M. Tamura, S.-i. Hayashi, K. Okamura, H. Sasano, and N. Yaegashi Peroxisome Proliferator-Activated Receptor {gamma} and Growth Inhibition by Its Ligands in Uterine Endometrial Carcinoma. Clin. Cancer Res., July 15, 2006; 12(14): 4200 - 4208. [Abstract] [Full Text] [PDF]

				K. Ito, T. Suzuki, J.-i. Akahira, M. Sakuma, S. Saitou, S. Okamoto, H. Niikura, K. Okamura, N. Yaegashi, H. Sasano, et al. 14-3-3{sigma} in Endometrial Cancer-A Possible Prognostic Marker in Early-Stage Cancer Clin. Cancer Res., October 15, 2005; 11(20): 7384 - 7391. [Abstract] [Full Text] [PDF]

				A. Vienonen, S. Miettinen, M. Blauer, P. M. Martikainen, E. Tomas, P. K. Heinonen, and T. Ylikomi Expression of Nuclear Receptors and Cofacotrs in Human Endometrium and Myometrium Reproductive Sciences, February 1, 2004; 11(2): 104 - 112. [Abstract] [PDF]

				X.-H. Li, H. Li, Z.-J. Xiao, and Y.-S. Piao Divergent Effects of Retinoic Acids on the Expression of ER{alpha} and 17{beta}-Hydroxysteroid Dehydrogenase Type 2 in Endometrial Carcinoma Cells (RL 95-2) J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 640 - 649. [Abstract] [Full Text] [PDF]