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 hvo othe r HCH-isomers, alpha and delta-HCH, inhibit steroidogenesis in a Y1 ad renocortical cell line. In determining the mechanism by which HCH isom ers inhibit steroidogenesis, they were found not to act directly on th e mitochondrial Cyt P-450scc enzyme, making it likely that they act, i nstead, 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) whi ch, in turn, is reported to regulate the rate-limiting step in steroid ogenesis. Although these results demonstrate that alpha and delta-HCH do not inhibit steroid production through the PBBS, the possibility th at the interaction of gamma-KCH with the PBBS is responsible for its i nhibitory effect on steroidogenesis could not be excluded.