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

Hongdan Zhang; Wei Wang; Zaichao Wu; Yuxiang Zheng; Xiao Li; Suo Han; Jing Wang; Chunping Zhang

doi:10.2174/1871530323666230418113852

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

Endocr Metab Immune Disord Drug Targets. 2023 Apr 18. doi: 10.2174/1871530323666230418113852. Online ahead of print.

Authors

Hongdan Zhang¹, Wei Wang², Zaichao Wu², Yuxiang Zheng², Xiao Li³, Suo Han³, Jing Wang¹, Chunping Zhang³

Affiliations

¹ Department of Microbiology, Jiangxi Medicine School, Nanchang University, Nanchang, China.
² Joint Programme of Nanchang University and Queen Mary University of London, Jiangxi Medicine School, Nanchang University, Nanchang, China.
³ Department of Cell Biology, Jiangxi Medicine School, Nanchang University, Nanchang, China.

PMID: 37106514
DOI: 10.2174/1871530323666230418113852

Abstract

Introduction: 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.

Method: 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.

Result: 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).

Keywords: 3?-HSD; Leydig cell; Notch; P450Scc; SF1; StAR.