Relationship:437
Contents
Key Event Relationship Overview
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Description of Relationship
Upstream Event | Downstream Event/Outcome |
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Translator protein (TSPO), Decrease | Cholesterol transport in mitochondria, Reduction |
AOPs Referencing Relationship
AOP Name | Type of Relationship | Weight of Evidence | Quantitative Understanding |
---|---|---|---|
PPAR alpha activation leading to decreased fertility upon utero exposure in rodent males | Directly Leads to | Moderate | |
PPARα activation leading to impaired fertility in adult male rodents | Directly Leads to | Moderate |
Taxonomic Applicability
Name | Scientific Name | Evidence | Links |
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How Does This Key Event Relationship Work
Translocator Protein (TSPO) mediates the first step in the delivery of cholesterol to the inner mitochondrial membrane cytochrome P-450 side chain cleavage enzyme(P450scc) (Besman et al., 1989). TSPO ligands stimulate steroidogenesis and induce cholesterol movement from the outer mitochondrial membrane (OMM) to the inner mitochondrial membrane (IMM) (Besman et al., 1989). Therefore reduced amount/activity of the TSPO will impair the cholesterol delivery necessary for the hormone biosynthesis.
Weight of Evidence
Biological Plausibility
Empirical Support for Linkage
The effects of altered TSPO are to decrease cholesterol transport into Leydig cells (Gazouli, 2002), (Borch, Metzdorff, Vinggaard, Brokken, & Dalgaard, 2006). Additionally, Thompson et al observed decreased uptake of cholesterol in Leydig cell mitochondria upon exposure to phthalates (Thompson, Ross, & Gaido, 2004).
Uncertainties or Inconsistencies
Quantitative Understanding of the Linkage
Is it known how much change in the first event is needed to impact the second? Are there known modulators of the response-response relationships? Are there models or extrapolation approaches that help describe those relationships?