Steroid receptor binding and messenger RNA expression in fibroids from untreated and gonadotrophin-releasing hormone agonist pretreated women.

Abstract

The hypothesis of this study was that oestrogen may play a role in fibroid growth and that a lack of oestrogen may be the reason for gonadotrophin-releasing hormone agonist (GnRHa) induced fibroid shrinkage. Therefore our aims were (1) to investigate oestrogen receptor (ER) and progesterone receptor (PR) binding in fibroids and myometrium from untreated women and in fibroids from GnRHa pretreated women, (2) to evaluate the mRNA expression of ER and PR in these tissues, and (3) to examine whether a correlation existed between receptor binding and mRNA expression for ER and PR. Cytosolic ER and PR binding was assessed by the dextran-coated charcoal technique and ER and PR mRNA expression was assessed using Northern blots of total RNA. Fibroid and corresponding myometrial specimens were obtained from 20 women undergoing hysterectomy while fibroid specimens only were obtained from 10 women undergoing myomectomy after at least 3 months pretreatment with GnRHa. We found that (1) ER binding was twice and PR binding was three times as great in fibroid as in myometrium and that there was no difference in binding for either receptor between fibroids from untreated and GnRHa pretreated women, (2) ER and PR mRNA abundances were similar in fibroids and myometrium from untreated women and in fibroids from untreated and GnRHa pretreated women, and (3) ER binding and ER mRNA abundance in both groups of fibroids and myometrium were independent of each other, but there was a positive correlation between PR binding and PR mRNA abundance in untreated fibroids and myometrium but not in GnRHa pretreated tumours. We conclude that (1) both oestrogen and progesterone may contribute to fibroid growth because of increased receptor binding in fibroids compared with myometrium and (2) in GnRHa treated women, fibroids may shrink because of a lowered circulating oestradiol level rather than because of a change in steroid receptor binding.