Article
Environmental Health Perspectives Volume 108, Number 8, August 2000

[ Citation in PubMed ] [ Related Articles ]

Roundup Inhibits Steroidogenesis by Disrupting Steroidogenic Acute Regulatory (StAR) Protein Expression

Lance P. Walsh,1 Chad McCormick,1 Clyde Martin,2 and Douglas M. Stocco1

1Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
2Department of Mathematics, Texas Tech University, Lubbock, Texas, USA

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 3ß-hydroxysteroid dehydrogenase (3ß-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. Key words: chemical mixtures, cytochrome P450 side chain cleavage, environmental endocrine disruptor, 3ß-hydroxysteroid dehydrogenase, Leydig cells, Roundup, steroid hormones, steroidogenesis, steroidogenic acute regulatory protein. Environ Health Perspect 108:769-776 (2000). [Online 12 July 2000]

http://ehpnet1.niehs.nih.gov/docs/2000/108p769-776walsh/abstract.html

Address correspondence to D.M. Stocco, Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79409 USA. Telephone: (806) 743-2505. Fax: (806) 743-2990. E-mail: doug.stocco@ttmc.ttuhsc.edu

We thank D. Alberts for technical assistance.

This work was supported by NIH grant HD17481 to D. Stucco. L. Walsh was supported by NIH grant T32-HD07271 and a scholarship from the Lubbock Achievement Awards for College Scientists Chapter.

Received 3 February 2000; accepted 11 April 2000.

[ Table of Contents ] [Full Article] [ Citation in PubMed ] [ Related Articles ]

Last Updated: July 12, 2000