Lp. Walsh et Dm. Stocco, Effects of lindane on steroidogenesis and steroidogenic acute regulatory protein expression, BIOL REPROD, 63(4), 2000, pp. 1024-1033
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.