The endometrium is a uniquely dynamic tissue in that it undergoes monthly cycles of proliferation and secretory activity, and is regulated by ovarian steroid hormones. In this study, we focused on retinoic acid receptors (RAR and RXR) which are ligand-dependent transcription factors belonging to the large family of steroid hormones and are expected to affect to cell growth and differentiation in the endometrium. We analysed the expression and subcellular localization of the RA receptors in 57 samples of human endometrium by immunohistochemistry and Western blotting. In the nuclei of the endometrial epithelium, the RA receptors were expressed strongly in the proliferative phase. However, RAR were drastically reduced in the epithelial nuclei during the secretory phase in association with changes in serum oestradiol and in the expression of the oestrogen receptor. The expression of RXR was localized in the epithelial nuclei throughout the menstrual cycle. Confocal laser scanning microscopical observation clearly showed the difference in the localization between RAR and RXR in the secretory phase. Furthermore the findings of immuno-electron microscopy showed pooled RAR around the rough endoplasmic reticulum, suggesting that transport of these receptors to the nuclei is inhibited. These findings suggest that RAR and RXR work mainly in the proliferative phase and that in the endometrium RXR may play a different role to RAR during the secretory phase.

Hyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression.

It is well known that the functions of reproductive organs are regulated by sex steroids and their receptors and it is hypothesized that the progression of neoplasms that originate from the reproductive organs is influenced by them. However, the correlation between sex steroids and tumor progression, especially tumor invasion, is not well known in endometrial carcinoma. In our study, we focused on the influence of estrogen and its receptor in invasion and matrix metalloproteinases (MMPs), which are known to be important in tumor invasion, as well as on endometrial carcinoma cells. The growth of Ishikawa cells, to which an estrogen receptor‐α expressing vector was transfected, was accelerated by 17β‐estradiol as was the acceleration of the expression of cyclin D1. By invasion assay, in conditions with 17β‐estradiol, the invasiveness of Ishikawa cells was enhanced. Furthermore, according to the accelerated invasiveness, the expression of MMP‐1, ‐7 and ‐9 and Ets‐1 was enhanced. These results suggest that activation of ER‐α by estrogen results in tumor progression by stimulating cell growth and invasiveness via acceleration of the expression of MMPs.