Hexachlorocyclohexanes inhibit steroidogenesis in Y1 cells. Absence of correlation with binding to the peripheral-type benzodiazepine binding site.
Lindane, the gamma-isomer of hexachlorocyclohexane (HCH), and two other HCH-isomers, alpha and delta-HCH, inhibit steroidogenesis in a Y1 adrenocortical cell line. In determining the mechanism by which HCH isomers inhibit steroidogenesis, they were found not to act directly on the mitochondrial Cyt P-450scc enzyme, making likely that they act, instead, on intramitochondrial transport of cholesterol. gamma-HCH, but not alpha or delta-HCH, is a potent and selective inhibitor of ligand binding to the peripheral-type benzodiazepine binding site (PBBS) which, in turn, is reported to regulate the rate-limiting step in steroidogenesis. Although these results demonstrate that alpha and delta-HCH do not inhibit steroid production through the PBBS, the possibility that the interaction of gamma-HCH with the PBBS is responsible for its inhibitory effect on steroid ogenesis could not be excluded.
Zisterer
D M
DM
Department of Biochemistry, Trinity College, Dublin, Ireland.
Moynagh
P N
PN
Williams
D C
DC
D000311:Adrenal Glands / Q000187:drug effects*; D000818:Animals; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D001556:Hexachlorocyclohexane / Q000494:pharmacology*; D051379:Mice; D011284:Pregnenolone / Q000378:metabolism; D011869:Radioligand Assay; D011963:Receptors, GABA-A / Q000187:drug effects
D011963:Receptors, GABA-A; D001556:Hexachlorocyclohexane; D011284:Pregnenolone