Dominant Expression of Progesterone Receptor Form B mRNA in Ovarian Endometriosis

Misao, Ryou; Iwagaki, Shigenori; Fujimoto, Jiro; Sun, Wen-Shu; Tamaya, Teruhiko

doi:10.1159/000023429

Cited by 36 publications

(28 citation statements)

References 20 publications

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“…PR-A and PR-B differ in that the PR-B protein contains an additional sequence of amino acids at its N-terminus, which has not been detected in PR-A [20,35]. The predominance of PR-B detected in RA synovial tissue in the present study is consistent with similar findings that have recently been reported in various tissues and their disorders, including ovarian endometriosis [36], metastatic lesions of gynaecologic cancers [37], human chordomas [38] and astrocytomas grades III and IV [39]. PR-B is generally considered more efficient as a transcriptional regulator than PR-A [40,41].…”

Section: Discussionsupporting

confidence: 90%

Sex steroid receptors in rheumatoid arthritis

et al. 2004

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Rheumatoid arthritis (RA) is a disease characterized primarily by chronic inflammatory synovitis and is well-known to be associated with significant sex differences in its prevalence and clinical features. Sex steroids have been proposed to be involved in the pathogenesis of RA, but details pertaining to the expression of sex steroid receptors in RA synovial tissue have yet to be fully characterized. In the present study, we examined oestrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR) and androgen receptor (AR) mRNA expression using real-time reverse transcriptase-PCR (RT-PCR) in eight female RA synovial tissues and six female synovial tissues without inflammation, and determined immunolocalization of ERalpha, ERbeta, PR-A, PR-B and AR using immunohistochemistry in synovial tissues obtained from 22 RA patients. Real-time RT-PCR analysis demonstrated the expression of ER, PR and AR mRNAs in both RA and non-inflamed synovial tissues. Relative abundance of ER mRNAs was significantly higher in RA synovial tissue than non-inflamed synovial tissue (P<0.05). In addition, the relative ERalpha/ERbeta mRNA expression ratio was significantly lower in RA than non-inflamed synovial tissue (RA, 2.34 +/- 1.60; and non-inflamed, 20.7 +/- 19.1; P<0.05). There were no significant differences in relative abundance of PR mRNA. Relative abundance of AR mRNA was significantly lower in RA (P<0.05). Immunoreactivity for ERalpha, ERbeta, PR-B and AR was detected in the lining cells, inflammatory cells and fibroblasts in all the patients examined. The labelling indices for ERbeta and PR-B were more abundant in both lining cells (ERbeta, 54.2 +/- 12.2%; PR-B, 73.6 +/- 18.9%) and inflammatory cells (ERbeta, 74.6 +/- 16.2%; PR-B, 75.9 +/- 16.1%) than in fibroblasts (ERbeta, 36.5 +/- 15.6%; PR-B, 49.4 +/- 18.0%). Labelling indices for ERalpha and AR were significantly higher in lining cells (ERalpha, 14.4 +/- 8.6%; AR, 31.2 +/- 11.3%) and fibroblasts (ERalpha, 12.1 +/- 7.5%; AR, 20.1 +/- 9.6%) than those in inflammatory cells (ERalpha, 5.7 +/- 3.3%; AR, 9.2 +/- 4.4%). There were significant differences (P<0.05) in the labelling indices for ERalpha, ERbeta and PR-B between men and women under 50 years of age in fibroblasts of RA synovial tissues. These results indicate that sex steroid receptors are present in RA and non-inflamed synovial tissues, including inflammatory cells in RA, and suggest that sex steroids may play important roles in the regulation of inflammation of RA synovial tissue.

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Section: Discussionsupporting

confidence: 90%

Sex steroid receptors in rheumatoid arthritis

et al. 2004

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“…[52][53][54][55] In human gynecological cancers, especially ovarian cancers, the dominant expression of PRB mRNA is a marker for a malignant phenotype. 56 With respect to endometriosis, Misao et al 57 showed that PRB mRNA is highly expressed in endometrioma. A recent study from Wu et al 58 demonstrated how knockdown of PRB can promote cell proliferation in immortalized endometrial stromal cells.…”

Section: Discussionmentioning

confidence: 99%

Disrupted Cell Cycle Control in Cultured Endometrial Cells from Patients with Endometriosis Harboring the Progesterone Receptor Polymorphism PROGINS

D’Amora

Maciel

Tambellini

et al. 2009

The American Journal of Pathology

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Presently, little is understood about how endometriosis is established or maintained, or how genetic factors can predispose women to the disease. Because of the crucial role that the progesterone receptor polymorphism PROGINS plays in predisposing women to the development of endometriosis, we hypothesized that this variant may influence critical steps during endometrial cell metabolism that are involved in the pathogenesis of endometriosis. Eutopic endometria were collected from three sources: women with endometriosis who had a single PROGINS allele (from the progesterone receptor gene); women with endometriosis who had the wild-type progesterone receptor allele; and women without endometriosis who had the wild-type allele. Cells prepared from the eutopic endometria of these women were stimulated with both estradiol and progesterone, and then examined for cell proliferation, viability, and apoptosis.

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“…PRA and PRB activation of gene transcription may have an important role in development of endometriosis. Since PRA dominantly acts as repressor of PRB, the ratio could be crucial (Misao et al, 1999). Unchanged PRAB expression observed in our study may thus mask differences in the PRB/PRA ratio, which may affect progesterone action in ovarian endometriomas.…”

Section: Resultsmentioning

confidence: 75%

“…The published data for the expression of ERs in endometriosis are rather contradictory. Matsuzaki et al (2001) reported no ERβ expression in 17% of ovarian endometriosis samples by TaqMan RT-PCR, while Fujimoto et al (1999) showed significantly higher expression of ERβ in ovarian endometriosis compared to normal endometrium. Recently, Bukulmez et al (2008) reported a significantly elevated ratio of ERβ/ERα mRNA in endometriomas, compared with eutopic endometrium, in agreement with our data.…”

Section: Resultsmentioning

confidence: 98%

“…These data show increased conversion of P into the biologically less active 20α-OHP, which has a lower affinity towards PRs, and which could be another way of enhancing E2 effects. The data on expression of PRs are also rather controversial: Misao et al (1999) have reported significantly higher levels of PRB mRNA in ovarian endometriosis samples compared to the normal endometrium. Attia et al (2000) have reported that PRB was not expressed in non-ovarian endometriosis, while Bukulmez et al (2008) detected three isoforms PRC, PRB and PRA in ovarian endometriomas.…”

Section: Resultsmentioning

confidence: 99%

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Disturbed estrogen and progesterone action in ovarian endometriosis

Šmuc

Hevir

Ribič-Pucelj

et al. 2009

Molecular and Cellular Endocrinology

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Please cite this article as:Šmuc, T., Hevir, N., Ribič-Pucelj, M., Husen, B., Thole, H., Rižner, T.L., Disturbed estrogen and progesterone action in ovarian endometriosis, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. SummaryEndometriosis is a very common disease in pre-menopausal women, where defective metabolism of steroid hormones plays an important role in its development and promotion. In the present study, we have examined the expression of 11 estrogen and progesterone metabolizing enzymes and their corresponding receptors in samples of ovarian endometriomas and control endometrium. Expression analysis revealed significant up-regulation of enzymes involved in estradiol formation (aromatase, sulfatase and all reductive 17β-hydroxysteroid dehydrogenases) and in progesterone inactivation (AKR1C1 and AKR1C3). Among the estrogen and progesterone receptors, ERα was down-regulated, ERβ was up-regulated, and there was no significant difference in expression of progesterone receptors A and B (PRAB). Our data indicate that several enzymes of estrogen and progesterone metabolism are aberrantly expressed in endometriosis, which can lead to increased local levels of mitogenic estradiol and decreased levels of protective progesterone. Changes in estrogen receptor expression suggest that estradiol may also act via non-estrogen-receptor-mediated pathways, while expression of progesterone receptors still needs further investigation.

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Dominant Expression of Progesterone Receptor Form B mRNA in Ovarian Endometriosis

Cited by 36 publications

References 20 publications

Sex steroid receptors in rheumatoid arthritis

Sex steroid receptors in rheumatoid arthritis

Disrupted Cell Cycle Control in Cultured Endometrial Cells from Patients with Endometriosis Harboring the Progesterone Receptor Polymorphism PROGINS

Disturbed estrogen and progesterone action in ovarian endometriosis

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