Effects of pubertal fenvalerate exposure on testosterone and estradiol synthesis and the expression of androgen and estrogen receptors in the developing brain.

ABSTRACT

Fenvalerate is a potential endocrine disruptor. Several studies have demonstrated that fenvalerate disrupts testosterone (T) synthesis in testes. T and estradiol (E(2)) are de novo synthesized in the developing brain. Thus, the aim of the present study was to investigate the effects of pubertal fenvalerate exposure on the synthesis of T and E(2) and the expression of androgen receptor (AR) and estrogen receptors (ERs) in cerebral cortex. CD-1 mice were orally administered daily with either vehicle or fenvalerate (7.5 or 30 mg/kg) from postnatal day (PND) 28 to PND56. The level of T and E(2) in cerebral cortex was significantly decreased in males exposed to fenvalerate. In agreement with the decrease in T and E(2) syntheses, the expression of 17ß-HSD, a key enzyme for T synthesis, was significantly reduced in cerebral cortex of fenvalerate-exposed males. Conversely, in females, the expression of 17ß-HSD in cerebral cortex was mildly up-regulated by fenvalerate and the level of T and E(2) was mildly increased. Pubertal fenvalerate exposure had no effect on the expression of StAR, P450(17α) and P450scc, the key enzymes for T synthesis, and P450 aromatase, the key enzyme for E(2) synthesis, in cerebral cortex of males and females. Interestingly, the expression of AR in cerebral cortex was up-regulated in male and female mice exposed to fenvalerate, whereas pubertal fenvalerate exposure did not affect the level of ERα and ERß in cerebral cortex. Taken together, these results suggest that pubertal fenvalerate exposure disrupts T and E(2) synthesis and the expression of AR in cerebral cortex. These changes of steroid status in the developing brain might be deleterious for neurobehavioral development.