Cellular defense mechanisms against benzo[a]pyrene in testicular leydig cells: Implications of p53, aryl-hydrocarbon receptor, and cytochrome p450 1A1 status

Jin Yong Chung, Young Kim Ji, Yoon Jae Kim, Ju Jung Sun, Ji Eun Park, Gee Lee Seung, Tac Kim Jin, Seunghoon Oh, Joo Lee Chang, Yong Dal Yoon, Hyun Yoo Young, Jong Min Kim

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Leydig cells of themammaliantestis produce testosterone and support spermatogenesis, and thereby their role in male function is fundamental. Although benzo[a]pyrene (B[a]P) has been known to exhibit carcinogenic, apoptogenic, and endocrine-disrupting activities, its potential signaling system in Leydig cells remains to be discovered. In the present study, using the TM3 Leydig cell line and primary Leydig cells, we showed that Leydig cells do not die by exposure to B[a]P and found that an increased level of X chromosome-linked inhibitor of apoptosis protein may be associated with the antiapoptotic process. The Leydig cells were shown to express p53, but its translational level was extremely low. Although a high level of p53 protein was not necessary for apoptosis induced by B[a]P-7,8-diol-9,10-epoxide (a final B[a]P metabolite) in Leydig cells, the apoptosis of primary Leydig cells appears to be p53 independent. This indicates the lack of p53 function in primary Leydig cells. Furthermore, Leydig cells were found to retain insignificant levels of endogenous aryl-hydrocarbon receptor and AhR nuclear transporter proteins in nature. Exposure to B[a]P did not result in a significant increase in aryl-hydrocarbon receptor proteins that are required for CYP1A1 transcription. CYP1A1 expression was present in Leydig cells but at levels insufficient to exhibit its activity. Finally, we have demonstrated that overexpression of CYP1A1 in Leydig cells sensitizes the cells to exhibit its activity in the presence of B[a]P and, thus, induction of apoptosis. Together, these results indicate that the deficiency of CYP1A1 activity might be a decisive condition rendering Leydig cells secure from exogenous polycyclic aromatic hydrocarbons such as B[a]P.

Original languageEnglish (US)
Pages (from-to)6134-6144
Number of pages11
JournalEndocrinology
Volume148
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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