Endocrine Disruptor MoA

Question 1

Mode of Action PCB

Answer 1

Polychlorinated biphenyls

• weak agonists of the oestrogen receptor
• at high concentrations may cause feminising effects
• at moderate concentrations may work more as an inhibitor - competing with oestrogen for binding sites

Question 2

Additional Reading - PCB

Answer 2

Matta et al., 1998

• O.mykiss early life stage exposure to different concentrations of PCB (1, 5, 20mg/L)
• accumulation of PCB was same in all treatments
• treatment exposure caused visible gonad abnormalities when compared to control
• levels of PCB in the fish were similar, if not lower than those found in field (2.1-2.5 micrograms)

Question 3

Mode of Action DDT

Answer 3

Anti-Androgen compound - binds to testosterone receptor and inhibits, causes similar effects to that of oestrogen

Question 4

Mode of Action TBT (probable)

Answer 4

Interference with steroid biosynthesis

• Studies have shown that oestrogen levels remain unaffected but levels of testosterone were high
• Assumed inhibition of conversion of testosterone to 17-Beta- oestradiol
• Inhibition of CYP19A1 enzyme aromatase (member of cytochrome P-450 superfamily responsible for catalysing many reactions in steroidogenesis)
• Use of aromatase inhibitors produced same results (imposex)

Question 5

Other Hypothesised Mode of Action TBT

Answer 5

TBT broken down in Phase I reaction in liver to produce TBT metabolites

• These metabolites may compete with testosterone for sulfur conjugation (Phase II reaction) therefore resulting in less testosterone being excreted
• This lack of excretion leads to a build up of testosterone