PARENT SESSION
PT2 - Endocrine Disruption
Tuesday, 19 November 2002
8:00 AM to 6:30 PM
Exhibit Hall

(P572) Mechanism of action of -sitosterol: impairment of cholesterol transfer across gonadal mitochondrial membranes.

MacLatchy, Deborah^*,1, Leusch, Frederic¹, Gilman, Christine¹, ¹ Canadian Rivers Institute, University of New Brunswick, Saint John, New Brunswick, Canada

ABSTRACT- It has been suggested that -sitosterol, a phytosterol found in high concentrations in pulp mill effluents, contributes to steroid depressions in fish living downstream of some mills. Previous studies have shown that -sitosterol's main locus of effect is at the level of cholesterol conversion to pregnolone, the rate-limiting step in steroidogenesis. Brook trout (Salvelinus fontinalis)and goldfish (Carassius auratus)were exposed to -sitosterol (150 g/g, silastic® implant)for >20d and gonadal mitochondria were isolated. Pregnenolone production was then measured in the mitochondrial preparations. In both species, -sitosterol had no effect on the activity of the P450scc enzyme that converts cholesterol to pregnenolone. Further experiments in goldfish, however, demonstrated that -sitosterol exposure decreased the size of the reactive pool of cholesterol available in the mitochondria for P450scc. This suggests that -sitosterol is impeding cholesterol transfer across the mitochondrial membrane resulting in depressed pregnenolone production. Further work is focusing on the mechanism by which cholesterol transfer is impaired.

Key words: fish, endocrine disruption, -sitosterol