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
Keywords:
Leydig cell, Notch, SF1, 3β-HSD, StAR, P450Scc.
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).
