Open Access

Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes

  • Authors:
    • Min Hu
    • Yuehui Zhang
    • Emil Egecioglu
    • Xin Li
    • Linus R. Shao
    • Håkan Billig
  • View Affiliations

  • Published online on: August 20, 2019     https://doi.org/10.3892/br.2019.1234
  • Pages: 135-144
  • Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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APA
Hu, M., Zhang, Y., Egecioglu, E., Li, X., Shao, L.R., & Billig, H. (2019). Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes. Biomedical Reports, 11, 135-144. https://doi.org/10.3892/br.2019.1234
MLA
Hu, M., Zhang, Y., Egecioglu, E., Li, X., Shao, L. R., Billig, H."Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes". Biomedical Reports 11.4 (2019): 135-144.
Chicago
Hu, M., Zhang, Y., Egecioglu, E., Li, X., Shao, L. R., Billig, H."Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes". Biomedical Reports 11, no. 4 (2019): 135-144. https://doi.org/10.3892/br.2019.1234