Numerous natural and anthropogenic chemicals interact with endocrine systems of
animals. The most widely studied of these endocrine active chemicals (EACs) are
estrogen receptor agonists and antagonists. Because of the many important roles of
estrogens in animals, xenoestrogens have the potential to impact environmental health. It
has been proposed that xenoestrogen contaminants are responsible for recent increases in
estrogen dependent human diseases and sexual and developmental abnormalities in
wildlife. Aquatic species are particularly susceptible to persistent EACs that accumulate in
sediments and biomagnify along trophic levels. Rainbow trout, Oncorhynchus mykiss,
commonly used in biomedical research and as a sentinel species, was chosen as a model
for studying mechanisms of xenoestrogen activity. The aims of this research were to
assess the estrogenic activity of individual persistent, organic contaminants and simple
mixtures in vivo. Emphasis was placed on determining the potential for xenoestrogens to
alter sexual development or to induce sexually dimorphic biochemical responses. Gonadal
abnormalities in trout exposed as embryos to the xenoestrogen o,p'-DDE showed that
xenobiotics can affect trout sexual development. However, the absence of endocrine
disruption by low doses of o,p'-DDE, by the xenoestrogens chlordecone and octylphenol,
or by the anti-androgen p,p'-DDE, suggested that lethality is likely to precede endocrine
disruption in highly exposed, feral salmonid populations. Sexually distinct responses in
immature trout were documented with respect to vitellogenin induction (2 to 4 fold higher
in females) and cytochrome P450 expression. Sex differences occurred only when doses
of estrogens or xenoestrogens were below levels that cause maximal estrogenic responses.
Evidence suggests that estrogen regulation may be fundamentally different in immature
males and females, which may have implications for natural populations exposed to
xenoestrogens. Vitellogenin induction and P450 modulation were responsive to mixtures
of estrogens and xenoestrogens in a manner suggestive of additive activation of estrogen
receptors. Cytochrome P450 dependent induction of lauric acid hydroxylation was
observed for the first time in trout, in response to tamoxifen and mixtures of tamoxifen
and 17��-estradiol. The estrogenic activity of tamoxifen and 4-hydroxy-2',4',6'-trichlorobiphenyl
were greater in vivo than what was predicted by in vitro studies, which
emphasized the need for mechanism based investigations of xenoestrogens in whole
organisms. / Graduation date: 1999
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/33325 |
| Date | 20 July 1998 |
| Creators | Carlson, David B., 1970- |
| Contributors | Williams, David E. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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