Protective effect of gomisin N on benzyl butyl phthalate-induced dysfunction of testosterone production in TM3 Leydig cells.

Abstract

Exposure to benzyl butyl phthalate (BBP) may induce disorders in the male reproductive system. However, the molecular mechanisms remain unknown. Here we investigated the effect of BBP on testosterone production and its molecular mechanisms. Furthermore, we also investigated the role of gomisin N (GN) from Schisandra chinensis (S. chinensis) in testosterone synthesis in TM3 Leydig cells. First, we examined the effects of BBP on expression levels of testosterone biosynthesis-related genes (StAR, CYP11α1, CYP17α1, 3βHSD, and 17βHSD) and attenuation-related genes (CYP1β1, CYP19α1, and Srd5α1-3). Although testosterone biosynthesis-related genes did not change, attenuation-related genes such as CYP1β1 and CYP19α1 were upregulated with ROS generation and testosterone level attenuation in the presence of 50 µM of BBP. However, the compound with the highest ROS and ONOO- scavenging activity from S. chinensis, GN, significantly reversed the expression of BBP-induced testosterone attenuation-related gene to normal levels. Subsequently, GN improved the testosterone production levels in TM3 Leydig cells. These events may be regulated by the antioxidant effect of GN. On conclusion, our study suggests, for the first time, that BBP impairs testosterone synthesis by the modulation of CYP1β1 and CYP19α1 expression in TM3 cells; GN could potentially minimize the BBP-induced dysfunction of TM3 cells to produce testosterone by suppressing CYP19α1 expression.