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Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia.

ABSTRACT: A delicate balance in estrogen and progesterone signaling through their cognate receptors is characteristic for the physiologic state of the endometrium, and a shift in receptor isotype expression can be frequently found in human endometrial pathology. In this study, using a transgenic mouse model, we examined the mechanisms whereby alterations in progesterone receptor (PR) isotype expression leads to endometrial pathology. For an experimental model, we used transgenic mice (PR-A transgenics) carrying an imbalance in the native ratio of the two PR isoforms A and B (PR-A and PR-B) through the expression of additional A form and examined their uterine phenotype under different hormonal regimens, using various criteria. Uterine epithelial cell proliferation was augmented in PR-A transgenics and was abolished by PR antagonists. In particular, proliferative response to progesterone, independent of signaling through estrogen, was enhanced. Upon continuous exposure to estradiol and progesterone, the uteri in PR-A transgenics displayed gross enlargement, endometrial hyperplasia including atypical lesions, endometritis and pelvic inflammatory disease. Imbalanced expression of the two isoforms of PR in a transgenic model reveals multiple derangements in the regulation of uterine physiology, resulting in various pathologies including hyperplasias.

SUBMITTER: Fleisch MC

PROVIDER: S-EPMC2657313 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

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Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia.

Fleisch M C MC Chou Y C YC Cardiff Robert D RD Asaithambi A A Shyamala G G

Molecular human reproduction 20090218 4

A delicate balance in estrogen and progesterone signaling through their cognate receptors is characteristic for the physiologic state of the endometrium, and a shift in receptor isotype expression can be frequently found in human endometrial pathology. In this study, using a transgenic mouse model, we examined the mechanisms whereby alterations in progesterone receptor (PR) isotype expression leads to endometrial pathology. For an experimental model, we used transgenic mice (PR-A transgenics) ca ...[more]

PMID: 19224949

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Project description:BACKGROUND:The value of the magnetic resonance imaging (MRI) in the assessment of women with endometrial hyperplasia and its role in diagnosis of myometrial invasion or coexistence of cancer is not known. This study aimed to evaluate the accuracy and usefulness of MRI in the management of patients diagnosed on endometrial biopsy with complex endometrial hyperplasia with atypia (CEHA). METHODS:A retrospective study of 86 cases diagnosed with endometrial hyperplasia with atypia on the initial endometrial biopsy in a tertiary university teaching hospital between 2010 and 2015 was carried out. The MRI accuracy in predicting malignant changes and influence the clinical management was compared among women who had either pelvic MRI, transvaginal ultrasound (TVUS), or no additional imagistic studies. RESULTS:MRI was performed in 24 (28%) and TVUS in 11 (13%)cases, while 51 (59%) women had no additional imagistic studies. In the group of women with no imaging studies, 26/51 (51%) were surgically treated and 8/26 (31%) were diagnosed with endometrial cancer (EEC) stage 1a. In the group of women who had TVUS, 5/11 (45%) were surgically treated and none was diagnosed with EEC. In the group of women who underwent an MRI examination, 20/24 (83%) were surgically treated. Among these, 11/20 (55%) were diagnosed with EEC, 7 had EEC stage 1a, and 4 had EEC stage 1b. Although MRI was able to identify malignant changes with a good sensitivity (91.7%), it had a low specificity in characterisation of malignant transformation (8%). MRI correctly identified 31% of the stage 1a and 33% of the stage 1b endometrial cancer. CONCLUSION:In this study, we found a potential diagnostic value of MRI for identifying malignant transformation in patients with CEHA. However, pelvic MRI has a rather weak predictive value of myometrial invasion in women with CEHA and concurrent EEC. The diagnostic and therapeutic benefits of MRI assessment in patients with CEHA need further validation.

Dataset Information

Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia.

Publications

Overexpression of progesterone receptor A isoform in mice leads to endometrial hyperproliferation, hyperplasia and atypia.

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