Autor: | Valérie Leblanc, Eric Asselin, Carl Shooner, Marie-Claude Dery |
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Rok vydání: | 2003 |
Předmět: |
endocrine system
medicine.medical_specialty Stromal cell Uterus Biology 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine Protein kinase B reproductive and urinary physiology 030304 developmental biology Estrous cycle 0303 health sciences TUNEL assay urogenital system Cell growth Obstetrics and Gynecology medicine.anatomical_structure Reproductive Medicine Apoptosis 030220 oncology & carcinogenesis Phosphorylation hormones hormone substitutes and hormone antagonists Developmental Biology |
Zdroj: | Reproductive Biology and Endocrinology. 1:47 |
ISSN: | 1477-7827 |
DOI: | 10.1186/1477-7827-1-47 |
Popis: | Molecular and intra-cellular mechanisms involved in the regulation of apoptosis processes in endometrial cells are poorly understood and documented. We have investigated the possibility that Akt survival pathway might be involved in the regulation of apoptosis in the uterus during the estrous cycle. Rats with regular estrous cycle (4 days) were killed at different days of estrous cycle (diestrus, proestrus, estrus and metestrus). Uteri were collected and fixed for immunohistochemical staining (IHC) and apoptotic cell death detection by [TdT]-mediated deoxyuridinetriphosphate nick end-labelling (TUNEL) or endometrial protein extracts collected for Western analysis. TUNEL analysis revealed that apoptosis was mainly found at estrus compared to other day of estrous cycle. TUNEL positive cells were apparent in luminal epithelial cells only. No apoptotic cells were observed at proestrus. In contrast, proliferation was maximal at proestrus as confirmed with the expression of CDC47/MCM7 (a cell proliferation marker). Intact form of caspase-3 was maximal at proestrus and was reduced only at estrus. Likewise, presence of a specific cleaved caspase-3 fragment was observed only at estrus and IHC revealed that cleaved caspase-3 signal was found in luminal epithelial cells. PTEN protein, a phosphatase involved in the regulation of Akt phosphorylation, was present at all days of estrous cycle and showed no significant regulation in relation to cycle. Expression of phospho-Akt (the activated form of Akt) was present at metestrus, diestrus, and proestrus but decreased significantly at estrus. Akt protein expression was maximal at estrus. IHC revealed that Akt expression was high in both stromal and epithelial cells at estrus. Further studies using ovariectomized rats demonstrated that 17β-estradiol increased endometrial cell proliferation which was accompanied by an increase of both Akt expression and phosphorylation. These results suggest that increased Akt expression and activity in response to estradiol may be an important mechanism to protect endometrial cells from apoptotic triggering and to induce endometrial cell proliferation, whereas inhibition of Akt activity leads to caspase-3 activation and apoptosis in endometrial cells. |
Databáze: | OpenAIRE |
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