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Citation
Tags
HERO ID
784768
Reference Type
Journal Article
Title
Decreased cytochrome c oxidase IV expression reduces steroidogenesis
Author(s)
Pawlak, KJ; Prasad, M; McKenzie, KA; Wiebe, JP; Gairola, CG; Whittal, RM; Bose, HS
Year
2011
Is Peer Reviewed?
Yes
Journal
Journal of Pharmacology and Experimental Therapeutics
ISSN:
0022-3565
EISSN:
1521-0103
Volume
338
Issue
2
Page Numbers
598-604
Language
English
PMID
21558439
DOI
10.1124/jpet.111.182634
Abstract
Steroidogenic acute regulatory protein facilitates the translocation of cholesterol to the inner mitochondrial membrane, thereby initiating steroidogenesis. At the inner mitochondrial membrane, cytochrome P450 side-chain cleavage enzyme converts cholesterol to pregnenolone, an oxidative process requiring electrons from NADPH. Pregnenolone then serves as the substrate for the formation of progesterone or dehydroepiandrosterone by downstream enzymes. Studies have shown that cigarette smoke (CS) influences steroid hormone levels. To better understand the underlying mechanisms, we used a mouse model to study the effects of chronic CS exposure on steroidogenesis. Through radioimmunoassay and metabolic conversion assays, we found that CS reduced progesterone and dehydroepiandrosterone without affecting cytochrome P450 side-chain cleavage enzyme or 3β-hydroxysteroid dehydrogenase 2 expression. However, CS did reduce expression of cytochrome c oxidase IV (COX IV), a component of the mitochondrial complex that serves as the last enzyme in the electron transport chain. Small interfering RNA-mediated COX IV knockdown indeed decreased progesterone synthesis in steroidogenic cells. In summary, COX IV likely plays a role in steroidogenesis, and passive smoking may negatively affect steroidogenesis by disrupting the electron transport chain.
Tag
IRIS
•
Dioxin (2012 Project Page for Final Report)
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