Abstract
Diethylstilbestrol (DES) is a synthetic oestrogen known to disrupt the endocrine system and to cause reproductive toxicity mediated via the hypothalamic-pituitary-adrenal axis; however, its molecular mechanism of action is poorly understood. In the present study, we found that, after only 1week of exposure to DES, blood testosterone dramatically decreased and that this decrease was associated with a strong induction of prolactin (PRL). Even with the increase in PRL, the luteinising hormone and follicle-stimulating hormone mRNAs slightly decreased. Our results show that, after 48hours of a single dose of DES, there was a six-fold increase in PRL expression. After exploring the upstream mechanisms, we determined that dopamine, which inhibits PRL secretion in male rats, did not decrease in the pituitary gland of DES-treated rats, whereas vasoactive intestinal peptide (VIP), which mediates the acute release of PRL, was elevated. Serotonin (5-HT) increased in the brain of male rats 24hours after a single DES treatment; however, PRL, VIP or 5-HT was not induced by DES in female rats. Our results indicate that DES induces the expression of pituitary PRL in male rats by stimulating VIP in the hypothalamus and 5-HT in the central nervous system.
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