Effects of lindane on steroidogenesis and steroidogenic acute regulatory protein expression

Lindane, the gamma isomer of hexachlorocyclohexane (HCH), is one of the old est synthetic pesticides still in use worldwide. Numerous reports have show n that this pesticide adversely affects reproductive function in animals. A lthough the pathogenesis of reproductive dysfunction is not yet fully under stood, recent reports indicate that lindane can directly inhibit adrenal an d 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 gamm a-HCH and its isomers, alpha-HCH and delta-HCH, on steroid production, ster oidogenic enzyme expression and activity, and steroidogenic acute regulator y (StAR) protein expression. StGR mediates the rate-limiting and acutely re gulated step in hormone-stimulated steroidogenesis, the intramitochondrial transfer of cholesterol to the P450(SCC) enzyme. Our studies demonstrate th at alpha-, delta-, and gamma-HCH inhibited dibutyryl ([Bu](2)) cAMP-stimula ted progesterone production in MA-10 cells in a dosage dependent manner wit hout affecting general protein synthesis; and protein kinase A or steroidog enic enzyme expression, activity, or both. In contrast, each of these isome rs dramatically reduced (Bu)(2)cAMP-stimulated StAR protein levels. Therefo re, our results are consistent with the hypothesis that alpha-, delta-, and gamma-HCH inhibited steroidogenesis by reducing StAR protein expression, a n action that may contribute to the pathogenesis of lindane-induced reprodu ctive dysfunction.