Effects of endocrine disrupters on the expression of growth hormone and prolactin mRNA in the rainbow trout pituitary.
It is now widely accepted that chemical pollutants in the environment can interfere with the endocrine system of animals, thus affecting development and reproduction. Some of these endocrine disrupters (EDs) can have estrogenic or antiestrogenic effects. Most studies to date have focused on the effects of EDs on the reproductive system and sex hormones and only limited information exists on how EDs may affect pituitary gland function. A rainbow trout (Oncorhynchus mykiss) pituitary gland culture system was used for studying the effects of EDs on growth hormone (GH) and prolactin (PRL) mRNA expression. We determined that the pituitary glands actively synthesized and secreted GH and PRL over the experimental time-course. In addition, we found that treatment with 17beta-estradiol (positive control) increased levels of GH and PRL mRNA, in a concentration-dependent manner. Treatment of pituitary glands with 500 and 1000 nM of a xenoestrogen, o,p'-DDT (o,p'-dichlorodiphenyltrichloroethane), resulted in a significant induction of GH and PRL mRNA, with a 20-fold increase for PRL and 3-fold increase for GH following treatment with 1000 nM o,p'-DDT. Co-incubation of pituitary glands with ICI 182 780 (a selective estrogen receptor antagonist) and o,p'-DDT resulted in inhibition of PRL mRNA levels; however, the stimulatory effect of DDT on GH mRNA was not seen in this experiment, nor was the inhibitory effect of ICI 182 780 observed with GH mRNA. To the contrary, ICI 182 780 (2.5 nM) had a stimulatory effect on GH mRNA levels. TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin), which is known to exert antiestrogenic effects, had an estrogenic-like effect that resulted in a concentration-dependent increase in the levels of GH and PRL mRNA. Co-incubation of pituitaries with TCDD and alpha-napthoflavone (ANF), which is an inhibitor of the aryl hydrocarbon receptor (AhR), caused an inhibition of TCDD-induced PRL mRNA at the higher and lower concentrations, but these effects were less consistent on GH mRNA levels. However, the responses of PRL and GH mRNA to co-incubation with TCDD and ANF, at the various concentrations, were bi-phasic wherein stimulation was seen at the low concentrations and inhibition at the high concentrations. Combined, these results suggest that o,p'-DDT and TCDD are xenoestrogens and that their effects on the expression of GH and PRL genes in the rainbow trout pituitary are modulated, in part, through the ER and AhR, respectively.
Elango
Anitha
A
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Shepherd
Brian
B
Chen
Thomas T
TT
D000818:Animals; D003634:DDT / Q000494:pharmacology*; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D008297:Male; D017686:Oncorhynchus mykiss / Q000235:genetics / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011388:Prolactin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D046509:Tissue Culture Techniques
D052244:Endocrine Disruptors; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D010908:Pituitary Hormones, Anterior; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D011388:Prolactin; D013006:Growth Hormone; D003634:DDT; C016340:o,p'-DDT