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1 October 2000 Effects of Lindane on Steroidogenesis and Steroidogenic Acute Regulatory Protein Expression
Lance P. Walsh, Douglas M. Stocco
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Lindane, the γ isomer of hexachlorocyclohexane (HCH), is one of the oldest synthetic pesticides still in use worldwide. Numerous reports have shown that this pesticide adversely affects reproductive function in animals. Although the pathogenesis of reproductive dysfunction is not yet fully understood, recent reports indicate that lindane can directly inhibit adrenal and gonadal steroidogenesis. Because Leydig cells play a pivotal role in male reproductive function through the production of testosterone, the mouse MA-10 Leydig tumor cell line was used to assess the potential effects of γ-HCH and its isomers, α-HCH and δ-HCH, on steroid production, steroidogenic enzyme expression and activity, and steroidogenic acute regulatory (StAR) protein expression. StAR mediates the rate-limiting and acutely regulated step in hormone-stimulated steroidogenesis, the intramitochondrial transfer of cholesterol to the P450scc enzyme. Our studies demonstrate that α-, δ-, and γ-HCH inhibited dibutyryl ([Bu]2) cAMP-stimulated progesterone production in MA-10 cells in a dosage-dependent manner without affecting general protein synthesis; and protein kinase A or steroidogenic enzyme expression, activity, or both. In contrast, each of these isomers dramatically reduced (Bu)2cAMP-stimulated StAR protein levels. Therefore, our results are consistent with the hypothesis that α-, δ-, and γ-HCH inhibited steroidogenesis by reducing StAR protein expression, an action that may contribute to the pathogenesis of lindane-induced reproductive dysfunction.

Lance P. Walsh and Douglas M. Stocco "Effects of Lindane on Steroidogenesis and Steroidogenic Acute Regulatory Protein Expression," Biology of Reproduction 63(4), 1024-1033, (1 October 2000).
Received: 1 March 2000; Accepted: 1 May 2000; Published: 1 October 2000
Leydig cells
male sexual function
signal transduction
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