Effect of Notch Signal Pathway on Steroid Synthesis Enzymes in TM3 Cells

Title:Effect of Notch Signal Pathway on Steroid Synthesis Enzymes in TM3 Cells

Volume: 23 Issue: 14

Author(s): Hongdan Zhang, Wei Wang, Zaichao Wu, Yuxiang Zheng, Xiao Li, Suo Han, Jing Wang and Chunping Zhang*

Affiliation:

• Department of Cell Biology, Jiangxi Medicine School, Nanchang University, Nanchang, China

Abstract:

Background: Studies have indicated that the conservative Notch pathway contributes to steroid hormone synthesis in the ovaries; however, its role in hormone synthesis of the testis remains unclear. We have previously reported Notch 1, 2, and 3 to be expressed in murine Leydig cells and that inhibition of Notch signaling caused G0/G1 arrest in TM3 Leydig cells.

Methods: In this study, we have further explored the effect of different Notch signal pathways on key steroidogenic enzymes in murine Leydig cells. TM3 cells were treated with Notch signaling pathway inhibitor MK-0752, and different Notch receptors were also overexpressed in TM3 cells.

Results: We evaluated the expression of key enzymes of steroid synthesis, including p450 cholesterol side-chain cleavage enzyme (P450Scc), 3β-hydroxysteroid dehydrogenase (3β-HSD) and steroidogenic acute regulatory protein (StAR), and key transcriptional factors for steroid synthesis, including steroidogenic factor 1 (SF1), GATA-binding protein 4 (GATA4) and GATA6.

Conclusion: We found the level of P450Scc, 3β-HSD, StAR and SF1 to be decreased after treatment with MK-0752, while overexpression of Notch1 up-regulated the expression of 3β-HSD, P450Scc, StAR and SF1. MK-0752 and overexpression of different Notch members had no influence on the expression of GATA4 and GATA6. In conclusion, Notch1 signaling may contribute to the steroid synthesis in Leydig cells through regulating SF1 and downstream steroidogenic enzymes (3β-HSD, StAR and P450Scc).

Cite this article as:

Zhang Hongdan, Wang Wei, Wu Zaichao, Zheng Yuxiang, Li Xiao, Han Suo, Wang Jing and Zhang Chunping*, Effect of Notch Signal Pathway on Steroid Synthesis Enzymes in TM3 Cells, Endocrine, Metabolic & Immune Disorders - Drug Targets 2023; 23 (14) . https://dx.doi.org/10.2174/1871530323666230418113852