PARENT SESSION

(W255) THE PPAR AGONIST GEMFIBROZIL MODULATES TESTOSTERONE PRODUCTION IN VITRO AND IN VIVO IN MALE GOLDFISH, Carassius auratus.

Cameron, Colin¹, Woodhouse, Amanda¹, Wenman, Christine¹, Moon, Thomas¹, Trudeau, Vance¹, ¹ University of Ottawa, Ottawa, ON, Canada

ABSTRACT- Gemfibrozil (GEM), a fibrate drug prescribed to lower blood triglycerides and an agonist of the peroxisome proliferator-activated receptor- (PPAR), has been detected in surface water. We investigated the possibility that GEM could disrupt testosterone (T) production in male goldfish. Goldfish testis fragments were cultured overnight to study basal and hCG-induced T secretion. The PPAR agonists, GEM and WY-14,643 (100 M), increased basal T secretion approximately 2-fold from testis fragments from goldfish approaching sexual maturity (March; pre-spawning). However, these PPAR agonists inhibited hCG-induced T production approximately 3-fold. In contrast, other PPAR agonists (bezafibrate and rosiglitazone) were without effect. GEM did not alter in vitro T secretion when sexually regressed fish (late June), or those undergoing early gonadal development (late November), were studied. In vivo experiments have also revealed effects of GEM on basal and hCG-induced T production. Waterborne GEM (1.5 mg/L) decreased plasma T concentrations in early November, while the same treatment in March resulted in increased T levels. In early June and September, GEM had no effect on basal plasma T levels, however, blunted responses of plasma T to hCG injections were observed in GEM exposed fish. Preliminary observations suggest that this effect may be related to parallel changes in the expression of testicular steroidogenic acute regulatory protein (StAR) mRNA. These results suggest that waterborne GEM may act as an endocrine disruptor. Funded by NSERC-DG and Strategic programs to TM and VT. CC and AW were supported by OGS.

KEY WORDS: Carassius auratus, PPAR, steroidogensis, EDC