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.

Progesterone receptor expression in the human placenta

“…Of importance to the present discussion is the observation that the predominant type of PR in the stromal nuclei during the secretory phase and early pregnancy is the A type, also observed by us. Additional support for the possibility that only the A form is predominantly present in certain situations comes from other studies (Viville et al, 1997) who have reported that A type dominated over B type in leiomyomata. There is only other report claiming that PR-B is not detectable (Boyd-Leinen et al, 1982), who reported the absence of PR-B in the oviduct of aged non-laying hens.…”

Etiology and pathogenesis of uterine leiomyomas: a review.

“…Both forms of PR (PR-A and PR-B) are expressed in leiomyomas and myometrium, with the concentration of PR-A higher than that of PR-B in both tissues (Viville et al 1997). In one study PR-A levels were increased in leiomyomata compared with the matched myometrium (Brandon et al 1993).…”

“…In the majority of the studies reviewed, the concentrations of both the ERs and PRs were greater in leiomyomata than the myometrium Brandon et al 1993Brandon et al , 1995Buchi and Keller 1983;Eiletz et al 1980;Englund et al 1998;Kawaguchi et al 1991;Lessl et al 1997;Marugo et al 1989;Nisolle et al 1999;Otsuka et al 1989;Pollow et al 1978a;Puukka et al 1976;Rein et al 1990c;Sadan et al 1987;Soules and McCarty 1982;Tamaya et al 1979Tamaya et al , 1985Vij et al 1990;Viville et al 1997;Vollenhoven et al 1994;Wilson et al 1980). In addition, Sadan et al found the ER and PR to be elevated in fibroids during all phases of the menstrual cycle when compared with matched myometria (Sadan et al 1987).…”

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

“…Both PR isoforms have been shown in human myometrium and leiomyoma, without any significant variation during the menstrual cycle phases (10). However, in leiomyoma the PR expression is higher than in adjacent myometrium (10)(11)(12)(13), explaining the evidence that progesterone is critical for tumor growth via cell proliferation and extracellular matrix accumulation (14,15).…”