Effects Of Pubertal Fenvalerate Exposure On Endocrine Disruption In Cerebral Cortex Of Mice

Objective The present study was to investigate the effects of pubertal fenvalerate exposure on the synthesis of testosterone (T) and estradiol (E2)and the expression of andogen receptor (AR) and estrogen receptors (ERα和ERβ) in cerebral cortex of mice. The current results might provide the basis for the molecular mechanism of fenvalerate-induced neurobehavioral developmental alterations in mice.Methods After quarantine and acclimation for one week, three-week-old mice were randomly divided into three groups, namely the control group, low-dose fenvalerate group and high-dose fenvalerate group. Male and female mice in fenvalerate groups were treated with fenvalerate (7.5 and 30 mg/kg) by gavage daily from postnatal day (PND) 28 to PND56. The controls received corn oil. Twelve mice (six males and six females) each group were killed at PND42. The remaining mice (twelve males and twelve females each group) were sacrificed at PND56. The whole cerebral cortex was dissected. Half of cerebral cortex was used to measure T and E2 in cerebral cortex. The other cerebral cortex was collected to analyze the protein expression for steroidogenic acute regulatory protein (StAR),P450 side-chain cleavage enzyme (P450scc), P450 17β-hydroxysteroid dehydrogenase (17β-HSD), 17α-hydroxylase enzyme (P45017α), cytochrome P450 19 (CYP19), AR, ERαand ERβby immunoblotting.Results The level of T and E2 in cerebral cortex was significantly decreased in males exposed to fenvalerate during puberty. In agreement with the decrease in T and E2 syntheses, the protein expression of 17β-HSD, a key enzyme for T synthesis, was significantly reduced in cerebral cortex of fenvalerate-exposed males. Conversely, in females, the protein expression of 17β-HSD in cerebral cortex was mildly up-regulated by fenvalerate and the level of T and E2 was mildly increased. Pubertal fenvalerate exposure had no effect on the protein expression of StAR,P450scc and P45017α, ie. the key enzymes for T synthesis, and P450 aromatase, the key enzyme for E2 synthesis, in cerebral cortex of males and females. Interestingly, the protein expression of AR in cerebral cortex was up-regulated in male and female mice exposed to fenvalerate during puberty, whereas pubertal fenvalerate exposure did not affect the level of ERαand ERβin cerebral cortex.Conclusion Puberdal fenvalerate exposure disrupts T and E2 synthesis and the expression of AR in cerebral cortex of mice. These changes of steroid status and its receptors in the developing brain might be deleterious for neurobehavioral development.