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Disrupting mitochondrial function with surfactants inhibits MA-10 Leydig cell steroidogenesis

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Abstract

It is well established that surfactants can elicit cytotoxic effects at threshold concentrations by changing the permeability and solubilizing components of cell membranes. The purpose of this study was to characterize the relationship between perturbation of the mitochondrial membrane resulting from treatment with representative cationic, nonionic, and anionic surfactants and the extent to which this perturbation affects steroid formation and StAR protein expression and activity in MA-10 Leydig cells. The StAR protein is synthesized as an active 37 kDa extramitochondrial form, which is processed into a 30 kDa intramitochondrial form after cholesterol transfer and mitochondrial import and processing. It has been shown in several in vitro studies that the mitochondrial electrochemical gradient is required for the StAR protein to transfer cholesterol to the inner mitochondrial membrane. Each substance that was tested produced a concentration-dependent decrease in steroid formation in hCG-stimulated MA-10 cells. Decreases in progesterone production were accompanied by loss of mitochondrial membrane potential and by a decrease in the levels of the 30 kDa form of the StAR protein. However, levels of the 37 kDa form of the StAR protein did not decrease, indicating no effect on StAR protein expression. These results demonstrate how perturbation of the mitochondrial membrane by surfactants inhibits import, processing, and cholesterol transfer activity and underscore the importance of including sensitive assays that evaluate mitochondrial function when screening for potential effects on steroidogenesis with in vitro test systems.

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Abbreviations

3β-HSD:

3β-hydroxysteroid dehydrogenase

DMEM:

Dulbecco’s modified Eagle’s medium

G3PDH:

glyceraldehyde–3–phosphate dehydrogenase

hCG:

human chorionic gonadotropin

HPLC:

high-performance liquid chromatography

IC50 :

median inhibitory concentration

LDH:

lactate dehydrogenase

MTT:

3–(4,5–dimethylthiazol–2–yl)–2,5–diphenyltetrazolium bromide

P450scc:

cytochrome P450 side-chain cleavage

PBS:

phosphate buffered saline

POEA:

polyoxyethylenealkylamine

RIA:

radioimmunoassay

StAR:

steroidogenic acute regulatory

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Authors and Affiliations

  1. Monsanto Company, Mail code: V2C, St. Louis, MO, 63167, USA

    S. L. Levine & D. R. Farmer

  2. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University Medical Center, Washington, DC, USA

    Z. Han, J. Liu & V. Papadopoulos

Authors
  1. S. L. Levine
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  2. Z. Han
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  3. J. Liu
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  4. D. R. Farmer
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  5. V. Papadopoulos
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Correspondence to S. L. Levine.

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Levine, S.L., Han, Z., Liu, J. et al. Disrupting mitochondrial function with surfactants inhibits MA-10 Leydig cell steroidogenesis. Cell Biol Toxicol 23, 385–400 (2007). https://doi.org/10.1007/s10565-007-9001-6

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  • DOI: https://doi.org/10.1007/s10565-007-9001-6

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