Studies on the expression of estrogen receptors (ERs) in uterine leiomyomata have yielded conflicting results. A controlled study focusing on leiomyomal nodules with same clinical presentations and hormonal milieu was conducted to investigate the role of ER beta (ERbeta) on leiomyomal growth. Thirty pairs of leiomyomal and myometrial tissues were included in the study. The specimens were obtained from 30 premenopausal women (40-45 years old) with parity 2, and were sampled during the proliferative menstrual phase. All of the leiomyomal nodules were unifocal, medium sized (4-5 cm), intramurally located, and without progressive enlargement for 6 months. The expressions of ERbeta mRNA and protein in leiomyomata and their adjacent myometria were analyzed by reverse transcriptase-polymerase chain reaction and immunohistochemistry using ERbeta-specific antibody, respectively. ER alpha (ERalpha) was simultaneously studied using similar methods. The results were digitally quantified and compared with each other. All paired tissues (30/30, 100%) showed a higher ERalpha expression level (paired t test, p < 0.05). In most leiomyomal nodules (27/30, 90%), both ERbeta and ERalpha exhibited no differences in mRNA levels compared to their adjacent myometria (p > 0.05), but the ratio of ERbeta/ERalpha (expression index) was lower (p < 0.05) in leiomyomal tissue. Although the immunoreactivity scores for ERbeta were similar in paired tissues, more ERbeta-positive cells were detected in myometrial specimens than in their leiomyoma counterparts (mean of 62% vs 56%). Furthermore, the distribution pattern of ERbeta in leiomyoma (nuclear and cytoplasmic) was different from that in the corresponding myometrium (nuclear). The lower ERbeta/ERalpha expression index in stationary leiomyoma suggests that the relative abundance of ERbeta and ERalpha, rather than their individual amounts, determines the existence and development of leiomyoma. This study demonstrated that in premenopausal women, ERbeta is not increasingly expressed in the leiomyomal nodules which show no progressive enlargement. The distinctive ERbeta-to-ERalpha ratio rather than their individual amounts, is associated with the stationary status of the leiomyomal nodule.
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