Distribution of the A and B forms of the progesterone receptor messenger ribonucleic acid and protein in uterine leiomyomata and adjacent myometrium.

Abstract

The two forms of the progesterone receptor, PR-A and PR-B, are independently regulated at the transcriptional level, and show distinct responses to progesterone antagonists. We were interested in possible differences in the PR-A to PR-B ratio between uterine myometrium and leiomyomata (fibroid), that might influence the response of fibroids to progesterone agonists and antagonists, and thus have consequences for the treatment of this condition. Fibroid and adjacent normal myometrium were obtained from 11 women undergoing hysterectomy. Immunohistochemistry using a monoclonal antibody which recognizes both PR-A and PR-B showed exclusively nuclear staining, and this was stronger in the leiomyomata than in adjacent myometrium. An antibody specific for PR-B gave fainter staining of both tissues. Western blotting confirmed a higher concentration of PR in leiomyomata than myometrium in eight out of 11 cases. In all cases both forms were present, with a consistent dominance of PR-A over PR-B. However an RNase protection assay showed that there was no difference between the concentrations of mRNA encoding PR-A and PR-B, or between the mRNA concentrations in leiomyomata and normal myometrium. We conclude that the observed differences between the levels of immunoreactive PR in leiomyomata and myometrium may result from post-translational control, and support the use of progesterone antagonists in the treatment of leiomyomata.