Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.
Analysis of cells for estrogen receptor-alpha and progesterone receptor proteins by Western blotting showed no change in expression of these proteins between the immortalized and parental leiomyoma and myometrial cells.
The present results imply that the increased ratio of ER alpha/ER beta observed in the fibroids after GnRHa treatment could reflect or be the cause of the shrinkage of the leiomyoma, which is the clinical outcome of this treatment.
Paradoxically, neither 17 beta-estradiol nor bFGF was capable of up-regulating Cyr61 mRNA in leiomyoma explants despite elevated levels of ER alpha mRNA, suggesting a possible defect in steroid and growth factor regulation.
This is likely because the myometrial and leiomyoma cells begin to express the novel ER-beta upon culturing, and agonist-bound ER-beta is known to inhibit AP-1 activity.
The results presented here suggest that some exogenous ER ligands may mimic the effects of endogenous estrogens on uterine leiomyoma and may contribute to a complex hormonal milieu that impacts both normal and neoplastic myometrium.
To shed light on the molecular mechanisms involved in the pathogenesis of uterine leiomyomas, transcript levels of the immediate early genes c-fos, c-myc, and c-jun and of the estrogen receptor (ER) and progesterone receptor (PR) were determined in tissue samples of human myometrium and leiomyoma.
We propose that increased expression of progesterone receptor in leiomyoma is most likely a consequence of overexpression of functional ER that results in increased end-organ sensitivity to estradiol.