Effects of levonorgestrel-releasing intrauterine system on the expression of steroid receptor coregulators TIF-2, AIB-1 and NCoR in adenomyosis

Abstract

Adenomyosis is a common benign gynecologic disease determined by the presence of endometrial glands and stroma located deep within the myometrium haphazardly. Recently the levonorgestrel-releasing intrauterine system (LNG-IUS) has been established as an effective medical treatment of adenomyosis by decreasing uterine bleeding, dysmenorrhea and uterine volume. Relatively high concentration of estrogen is thought to play a major role in the pathogenesis of adenomyosis. The steroid hormones such as estrogen are mediated via their receptors, and steroid receptors interact with steroid receptor coregulators. These factors bind to steroid receptors in a ligand-dependent fashion and then stimulate or suppress the transcription of target genes, the former coactivators and the latter corepressors. There have been no systematic studies on the expression of steroid receptor coregulators in adenomyosis, and the effect of LNG-IUS on the expression of these factors in adenomyosis has not been established. In the present study, the expressions of steroid receptor coregulators, Transcriptional intermediary factor-2 (TIF-2), amplified in breast cancer-1 (AIB-1) and nuclear receptor corepressor (NCoR) in endometrial tissues from control group, untreated adenomyosis group and LNG-IUS-treated adenomyosis group are immunohistochemically evaluated. Tissue samples of endometrium were obtained from 38 premenopausal women with symptomatic adenomyosis, and 23 normal ovulatory women who had carcinoma in situ of uterine cervix without any other significant uterine abnormalities after hysterectomy. Seventeen women with adenomyosis were treated with LNG-IUS. Immunostaining for TIF-2, AIB-1 and NCoR was performed and assessed semiquantitatively. TIF-2 was distributed diffusely in endometrial glandular cytoplasm and stromal cell irrespective of menstrual phase. The expression of TIF-2 in glandular and stromal cell showed strong intensity in the control group and untreated adenomyosis group. The endometrium from LNG-IUS-treated adenomyosis group demonstrates significantly decreased expression of TIF-2 compared with those from control group and untreated adenomyosis group. The expression of AIB-1 was observed diffusely in endometrial stromal cells and negligible in glandular cells. AIB-1 expression in stromal cell was greatest in untreated adenomyosis group. The endometrium from untreated adenomyosis group demonstrated significantly higher expression of AIB-1 compared with those from control group and LNG-IUS treated adenomyosis. The immunoreactivity of NCoR was observed in both endometrial glandular and stromal cell throughout the menstrual cycle. NCoR expressions in endometrial glandular nucleus were significantly decreased in untreated adenomyosis group compared with normal control group, and significantly increased in LNG-IUS-treated group compared with untreated adenomyosis group during the proliferative phase. Therefore, the alteration of expression of TIF-2, AIB-1 and NCoR in adenomyosis may be a possible underlying pathogenetic mechanism of adenomyosis and these coregulators may also be associated with the treatment mechanism of LNG-IUS in adenomyosis.