Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes
| Autor: | Linus R Shao, Håkan Billig, Xin Li, Min Hu, Emil Egecioglu, Yuehui Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.drug_class Estrogen receptor General Biochemistry Genetics and Molecular Biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Glycolysis General Pharmacology Toxicology and Pharmaceutics Hexokinase estrogen receptor subtypes uterus General Neuroscience Articles General Medicine glycolysis Polycystic ovary 030104 developmental biology Endocrinology chemistry polycystic ovary syndrome Estrogen 030220 oncology & carcinogenesis Knockout mouse knockout mice Pyruvate kinase Phosphofructokinase |
| Zdroj: | Biomedical Reports |
| ISSN: | 2049-9442 2049-9434 |
| DOI: | 10.3892/br.2019.1234 |
| Popis: | The estrogen signaling pathway via nuclear estrogen receptors (ER) α and β is considered to be the master regulator of the cellular glucose metabolism in the uterus. While in vivo animal studies have demonstrated that 17β-estradiol (E2) treatment increases the expression levels and activities of several glycolytic enzymes in the uterus, the specific ER subtype-dependent regulation of key glycolytic enzymes in the uterus has not been experimentally verified. In this study, the localization of ERα and ERβ in human and mouse endometria were evaluated using immunohistology. Given that ERα and ERβ are not functionally equivalent, ERα, ERβ and ERαβ knockout (ERα-/-, ERβ-/- and ERαβ-/-) mice were utilized to determine the expression pattern of glycolytic enzymes in the uterus. It was found that the level of ERα was higher than that of ERβ in the human and mouse endometrial epithelial and stromal cells, and both receptors were downregulated by E2 treatment in the mouse uterus. The expression of the hexokinase 1 and GAPDH was increased in ERα-/- and ERβ-/- mice compared with wild-type controls. Increased phosphofructokinase expression was observed in ERα-/- and ERαβ-/- mice, whereas increased pyruvate kinase isozyme M2 and pyruvate dehydrogenase expression was observed in ERβ-/- and ERαβ-/- mice. The findings indicated for the first time that while estrogen regulates ERα and ERβ expression in the uterus, ERα and ERβ selectively regulate uterine glycolytic enzyme expression during glycolysis. Additionally, the link between endometrial ER subtypes and glycolysis in women with polycystic ovary syndrome (PCOS) is discussed. The findings suggested that the E2-dependent ER-mediated regulation of glycolysis may be involved in the disturbance of the glucose metabolism in patients with PCOS with endometrial dysfunction. |
| Databáze: | OpenAIRE |
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