2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits prostatic epithelial bud formation by acting directly on the urogenital sinus.
OBJECTIVE
In utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure causes lobe specific inhibition of prostate development in C57BL/6 mice due primarily to region specific inhibition of prostatic epithelial bud formation by the urogenital sinus (UGS). This inhibition requires that the receptor for TCDD, the aryl hydrocarbon receptor (AhR), must be present. We tested the hypothesis that TCDD inhibits prostatic epithelial bud formation by acting directly on the UGS.


METHODS
UGSs were removed from WT and AhR null mutant (AhRKO) male C57BL/6 mice on gestation day 14 and incubated in vitro with vehicle, 10-8 M testosterone or 10-8 M testosterone plus 10-9 M TCDD for 5 days. Budding was evaluated by a newly developed technique, namely scanning electron microscopy of UGS epithelium after removal of UGS mesenchyme.


RESULTS
Few buds were present in UGSs of either genotype in the absence of testosterone, while many were observed when testosterone was present. TCDD prevented prostatic epithelial buds from forming in UGSs from WT mice but it had no effect on UGSs from AhRKO mice.


CONCLUSIONS
TCDD can act directly on the UGS to cause AhR dependent inhibition of prostatic epithelial bud formation. Because this inhibition occurred at a TCDD concentration similar to the estimated concentration at which TCDD inhibits bud formation in vivo, it appears that TCDD inhibits prostatic budding primarily via direct effects on the UGS rather than indirectly through effects on other organs.
Lin
Tien-Min
TM
School of Pharmacy, Molecular and Environmental Toxicology Center and Department of Animal Sciences, University of Wisconsin, Madison, Wisconsin 53726-4087, USA.
Rasmussen
Nathan T
NT
Moore
Robert W
RW
Albrecht
Ralph M
RM
Peterson
Richard E
RE
D000818:Animals; D003470:Culture Media; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011467:Prostate / Q000002:abnormalities* / Q000187:drug effects*; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects* / Q000235:genetics; D013723:Teratogens / Q000494:pharmacology*; D014566:Urogenital System / Q000187:drug effects*
D003470:Culture Media; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens