Disruption of the rainbow trout reproductive endocrine axis by the polycyclic aromatic hydrocarbon benzo[a]pyrene

Successful reproduction in salmonids depends on a complex and highly regulated interplay between the pharmacokinetics and pharmacodynamics of naturally circulating sex steroids. The effects of a single intraperitoneal administration of the model PAH benzo[a]pyrene (B[a]P) on the kinetics of circulating levels of estradiol and testosterone through 7d post-injection in mature male and female rainbow trout (Oncorhynchus mykiss) in pre-spawning and spawning condition were investigated. Detailed measurements of the time course of injected E2 and excretion into the bile followed by pharmacokinetic modeling techniques were used to aid in identifying the potential mechanism of ED caused by B[a]P exposure. Plasma E2 and T concentrations were reduced significantly in both male and female trout. Administration of the GnRH analogue des-Gly(10)[D-Ala(6)]LH-RH-ethylamide, to induce spawning steroid profiles increased plasma E2 concentrations in control females, but not in B[a]P-treated fish. The mechanism underlying reductions in sex steroids in pre-spawning and spawning salmonids appears to be unrelated to the induction of P450 and related biotransformation enzymes by B[a]P. Induced biotransformation enzyme activities did not result in altered [(3)H]estradiol pharmacokinetics (e.g. terminal half-life) or elimination of steroid in bile, suggesting that B[a]P alters plasma E2 and T concentrations by other ED mechanisms in an anti-estrogenic manner.