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The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 6 2721-2727
Copyright © 2001 by The Endocrine Society

Other Original Studies

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

Kiyoshi Ito, Takashi Suzuki, Takuya Moriya, Hiroki Utsunomiya, Akira Sugawara, Ryo Konno, Shinji Sato and Hironobu Sasano

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 {alpha}, ß, and {gamma}, and retinoid X receptor (RXR) {alpha}, ß, and {gamma} 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{gamma} 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{gamma} 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{gamma} labeling index (LI) (P < 0.001) and between RXR{gamma} LI and progesterone receptor LI (r = 0.501, P = 0.003).

A significant inverse correlation was also detected between RXR{gamma} 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{gamma} by stimulating the expression of 17ß-HSD type 2.




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