Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression.

Abstract

Recent reports demonstrate that many currently used pesticides have the capacity to disrupt reproductive function in animals. Although this reproductive dysfunction is typically characterized by alterations in serum steroid hormone levels, disruptions in spermatogenesis, and loss of fertility, the mechanisms involved in pesticide-induced infertility remain unclear. Because testicular Leydig cells play a crucial role in male reproductive function by producing testosterone, we used the mouse MA-10 Leydig tumor cell line to study the molecular events involved in pesticide-induced alterations in steroid hormone biosynthesis. We previously showed that the organochlorine insecticide lindane and the organophosphate insecticide Dimethoate directly inhibit steroidogenesis in Leydig cells by disrupting expression of the steroidogenic acute regulatory (StAR) protein. StAR protein mediates the rate-limiting and acutely regulated step in steroidogenesis, the transfer of cholesterol from the outer to the inner mitochondrial membrane where the cytochrome P450 side chain cleavage (P450scc) enzyme initiates the synthesis of all steroid hormones. In the present study, we screened eight currently used pesticide formulations for their ability to inhibit steroidogenesis, concentrating on their effects on StAR expression in MA-10 cells. In addition, we determined the effects of these compounds on the levels and activities of the P450scc enzyme (which converts cholesterol to pregnenolone) and the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme (which converts pregnenolone to progesterone). Of the pesticides screened, only the pesticide Roundup inhibited dibutyryl [(Bu)(2)]cAMP-stimulated progesterone production in MA-10 cells without causing cellular toxicity. Roundup inhibited steroidogenesis by disrupting StAR protein expression, further demonstrating the susceptibility of StAR to environmental pollutants.

Cited by papers we hold 8

• Protective Effect of Resveratrol on Benzo(a)Pyrene Induced Dysfunctions of Steroidogenesis and Steroidogenic Acute Regulatory Gene Expression in Leydig Cells · 2019
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• Glyphosate Residues in Groundwater, Drinking Water and Urine of Subsistence Farmers from Intensive Agriculture Localities: A Survey in Hopelchén, Campeche, Mexico · 2017
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• Concerns over use of glyphosate-based herbicides and risks associated with exposures: a consensus statement · 2016
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• Transcriptome profile analysis reflects rat liver and kidney damage following chronic ultra-low dose Roundup exposure · 2015
  Corrected
• Major Pesticides Are More Toxic to Human Cells Than Their Declared Active Principles · 2014
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• Unidentified Inert Ingredients in Pesticides: Implications for Human and Environmental Health · 2006
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• Differential Effects of Glyphosate and Roundup on Human Placental Cells and Aromatase · 2005
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• Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study · 2004
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