1. Academic Validation
  2. Dihydrotestosterone regulation of cyclooxygenase-2 expression in bovine endometrial epithelium cells by androgen receptor mediated EGFR/PI3K/Akt pathway

Dihydrotestosterone regulation of cyclooxygenase-2 expression in bovine endometrial epithelium cells by androgen receptor mediated EGFR/PI3K/Akt pathway

  • J Steroid Biochem Mol Biol. 2021 Nov;214:106001. doi: 10.1016/j.jsbmb.2021.106001.
Longfei Xiao 1 Wanxu Sun 1 Yue Su 1 Ning Lu 1 Yanan He 2 Xihui Sheng 1 Xiaolong Qi 1 Kai Xing 1 Yong Guo 1 Di Chang 1 Xiangguo Wang 3 Junjin Zhao 4 Hemin Ni 5
Affiliations

Affiliations

  • 1 Animal Science and Technology College, Beijing University of Agriculture, Beijing, China.
  • 2 Zhangjiagang Agriculture and Rural Affairs Bureau, Jiangsu, China.
  • 3 Animal Science and Technology College, Beijing University of Agriculture, Beijing, China. Electronic address: xiangguo731@bua.edu.cn.
  • 4 National Grazing Headquarter, Beijing, China.
  • 5 Animal Science and Technology College, Beijing University of Agriculture, Beijing, China. Electronic address: nihemin@aliyun.com.
Abstract

Uterine prostaglandins F2α (PGF2α) is essential for implantation, initiation of luteolysis and delivery. Previous studies have demonstrated that the expression of Cyclooxygenase-2 (COX-2), an Enzyme limiting PGF2α rate, is regulated by steroid Hormones, and also dihydrotestosterone (DHT) may be involved in regulating COX-2 expression both positively and negatively. However, it remains unclear how whether DHT regulates COX-2 expression and consequent PGF2α release in bovine endometrial epithelial cells (EECs). In this study, we evaluated the localization of the two isoforms of DHT synthetase 5α-reductase (5α-red1 and 5α-red2) and Androgen Receptor (AR) in bovine endometria by immunohistochemistry, and investigated 5α-red1, 5α-red2, AR, and DHT levels at the different stages of endometria (follicle, early-, mid-, and late-pregnancy phases). The results showed that 5α-red1, 5α-red2 and AR all were expressed in endometria, and their expressions and the level of DHT significantly increased in the late-pregnancy phase compared with the mid-pregnancy phase. Moreover, we cultured EECs from the mid-pregnancy phase and the in vitro study showed that DHT dose-dependently increased COX-2 expression and PGF2a release, but AR antagonist (flutamide) inhibited the stimulating effect via DHT. In addition, the DHT-induced COX-2 expression and PGF2α release were subjected to the regulation of both EGFR/PI3K/Akt/NFkB signaling as the inhibitors of EGFR (AG1478) and PI3K/Akt (LY294002) and NFkB (QNZ) attenuated the DHT mediated effect. Taken together, the results demonstrated that DHT-induced COX-2 expression and consequent PGF2α release in bovine EECs were mediated through AR-derived EGFR transactivation and PI3K/Akt cascade leading to NFkB activation.

Keywords

Cyclooxygenase-2; Dihydrotestosterone; EGFR; Endometria; Endometrial epithelial cells.

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