Title

Effects of endocrine disruptors on rainbow trout pituitary gland function

Date of Completion

January 2004

Keywords

Biology, Molecular|Biology, Cell|Health Sciences, Toxicology

Degree

Ph.D.

Abstract

It is now widely accepted that chemical pollutants in the environment can interfere with the hormonal systems of animals, thus affecting development and reproduction. Some of these endocrine disrupters (EDs) can be estrogen mimetics or have antiestrogenic effects. Most studies to date have focused on the effects of EDs on the gonadal system and sex hormones and only limited information exists on how EDs may affect pituitary gland function. In this dissertation, a pituitary gland culture system was validated for studying the effects of endocrine disrupters on synthesis and secretion of growth hormone (GH) and prolactin (PRL). The pituitary glands maintained in culture were actively synthesizing and secreting pituitary hormones, and were responsive to treatment with 17β-estradiol by elevating the levels of GH and PRL mRNA in a dose-dependent manner. Treatment of pituitary glands in culture with 1μM of a xenoestrogen, o,p-DDT ( o,p-dichlorodiphenyltrichloroethane), resulted in a 20-fold increase of PRL mRNA and a 3-fold increase of GH mRNA over controls. Co-incubation of pituitary glands with ICI 182 780 (an estrogen receptor antagonist) resulted in inhibition of o,p-DDT induced PRL mRNA, but this inhibitory effect was not observed for GH. These results suggest that binding of o,p-DDT to the estrogen receptor (ER) in the pituitary gland may be required for the induction of PRL mRNA but not for the induction of GH. ^ 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), which is known to exert antiestrogenic effects, had a biphasic effect on the levels of GH and PRL mRNA, with a slight inhibition at the lower concentrations and a dose-dependent increase at higher concentrations. Alphanapthoflavone (ANF, an AhR antagonist), caused an inhibition of TCDD induced PRL mRNA but to a lesser extent on TCDD induced GH mRNA at both higher and lower concentrations. These results suggest that the effects of TCDD on rainbow trout pituitary glands are modulated through the Ah receptor. Our results indicate that endocrine disrupters affect pituitary gland function by altering the expression of GH and PRL genes likely via both ER and non-ER mediated pathways. Furthermore, this in vitro pituitary gland culture system may be used to monitor the effects of environmental xenobiotics on the pituitary hormone axis. ^