1. Academic Validation
  2. Estrogen and glucocorticoid promote the lactoferrin synthesis and secretion ability of bovine mammary epithelial cells through ER and GR signaling pathways

Estrogen and glucocorticoid promote the lactoferrin synthesis and secretion ability of bovine mammary epithelial cells through ER and GR signaling pathways

  • Int J Biol Macromol. 2025 Feb 2:140636. doi: 10.1016/j.ijbiomac.2025.140636.
Yuejie Yang 1 Xinru Li 1 Yandi Wang 1 Jianhui Wang 1 Guichi Liu 1 Zijian Geng 1 Rui Wu 2 Shuai Lian 3 Jianfa Wang 4
Affiliations

Affiliations

  • 1 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China; China Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing 163319, China; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing 163319, China.
  • 2 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China; China Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing 163319, China; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing 163319, China; College of Biology and Agriculture, Jiamusi University, Jiamusi 154007, China.
  • 3 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China; China Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing 163319, China; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing 163319, China. Electronic address: lianshuai@byau.edu.cn.
  • 4 College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163319, China; China Key Laboratory of Bovine Disease Control in Northeast China, Ministry of Agriculture and Rural Affairs, Daqing 163319, China; Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, Daqing 163319, China. Electronic address: wjflw@sina.com.
Abstract

Lactoferrin (LF) is an innate immunity glycoprotein with Antibacterial, anti-inflammatory, Antiviral, anti-tumor, and autoantibody activity-enhancing properties. Steroid Hormones are essential for development and lactation in the dairy cow mammary gland, and act through binding to receptors that drive gene transcription. However, it remains unclear whether steroid hormone receptors play roles in LF synthesis in bovine mammary epithelial cells (BMECs). In this study, we investigated the direct effects of estrogen and glucocorticoid on LF synthesis and secretion by BMECs. The results show that treatment of BMECs with estrogen (17-β-estradiol, E2) and glucocorticoid (hydrocortisone) significantly promoted cell proliferation. Furthermore, E2 or hydrocortisone increased the expression levels of Estrogen Receptor (ER) and Glucocorticoid Receptor (GR), and stimulated the synthesis and secretion of LF in BMECs. Treatment of BMECs with various inhibitors (fulvestrant, mifepristone, and pimozide) decreased LF gene transcript and LF protein levels. It was concluded that fulvestrant and mifepristone inhibit LF transcription and translation via inhibiting ER and GR, respectively. Our data indicate that E2 and hydrocortisone regulate LF protein synthesis through the ER and GR signaling pathways. These results provide new information about the regulation of the synthesis of functional proteins in milk.

Keywords

Bovine mammary epithelial cells; Estrogen; Gene expression regulation; Glucocorticoid; Lactoferrin.

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