what are we learning from wildlife about endocrine disruption that is relevant to human health?

What are we learning from wildlife about endocrine disruption that is

relevant to human health? Dr. Peter L. deFurCenter for Environmental StudiesVirginia Commonwealth UnivJune 20 2013

In A Word

EverythingWell…

Almost everythingConsidering all “not people” animals

Pesticide companies have disrupted insect hormone systems for ca. 40 years

All good science is a story – of inquiry and discovery Hormonal control of metamorphosis in insects is affected by molting (ecdysone) and juvenile hormones

OH

HO

HOH

O

OH

OH

OHOH

HO

HOH

O

OH

OH

OHOH

HO

HOH

O

OH

OHOH

OH

HO

HOH

O

OH

Ponasterone A

20-HydroxyecdysoneEcdysone

Makinsterone A

OH

HO

HO

OH

OHO

3-dehydroecdysone

OH

HO

HOH

O

OH

25-deoxyecdysoneInsect Juvenile Hormone

Tebufenozide

Ecdysone

O

O

OO

O

O

O

OO

JH-I

JH-II

JH-IIIOO

O

JH-III bis epoxide

O

O

O

methyl farnesoate

OO

O

O

ONH O

O

O

OO N

Methoprene

Fenoxycarb

Pyriproxyfen

O

O

Hydroprene

Two clutches of eggs in one nestCross-billed cormorant In 1993-

6

The Story continues- pick up to the early 1990’s

Beginning with

wildlife in recent years

Mimic normal action Abnormal action Blocked action

hormone

hormone

EDC EDC

EDC

R

R R

R= hormone receptor; EDC = endocrine disrupting chemical

Model of how EDC acts on hormone-receptor interactions

What can go wrong or awry with chemicals in the environment?

Fish sex change

First reported in Florida in 1970’s Male Goby fish showed female characteristics Downstream from pulp mill effluent Sitosterol was active chemical from trees Reported in other rivers with pulp effluent Resurfaced in England in 1995- thanks to

John Sumpter

“steroid” mechanism of action

Second messenger mechanism

How does a system work?

Lessons thus far

Can synthesize hormones and mimics Untimely exposures can harm Endogenous hormones when exogenous— Mechanisms and processes Low levels can harm

Ecy receptor

RxR receptor

17B-Estradiol 20- hydroxyecdysone Diethylstilbestrol (DES)

DDT Coumestrol

BPA

4-nonylphenol17 B estradiol

chlordecone

Tributyltin

Ah receptor model

Lessons learned- some too late

Biology is conserved What can go wrong How disruption occurs New end points New mechanisms Indicators- the canary in the coal mine Need confirmation from mammalian data

Summary of lessons

Birds Reproduction, developmentBehaviour

PCB, TCDD, Cl-

Mammals Reproductiondevelopment

Chlorinated chem.’s

FishAmphibian

Sex determination EE, E, T, A

Invert.’s cross species; growth, development

Juvenile mimics; TBT;

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