Contaminant-Induced Changes in Hepatic Steroid Hormone DegradationEPA Grant Number: R824760
Title: Contaminant-Induced Changes in Hepatic Steroid Hormone Degradation
Investigators: Guillette Jr., Louis J.
Institution: University of Florida
EPA Project Officer: Hahn, Intaek
Project Period: October 1, 1995 through September 1, 1998
Project Amount: $407,679
RFA: Human Health Risk Assessment (1995) RFA Text | Recipients Lists
Research Category: Economics and Decision Sciences , Health Effects , Human Health , Human Health Risk Assessment , Health
Description:The purpose of this research is to demonstrate that reptiles are excellent sentinel species for the health of wetlands. In particular, that they can be used to assess the presence of endocrine disrupting contaminants (EDCs). Others have demonstrated that exposure of reptiles to EDCs (naturally and experimentally) alters the morphology of the gonad, causes sex reversal and/or hermaphroditism, and dramatically alters the plasma concentrations of circulating steroid hormones. Also, it has been observed that the altered plasma estradiol and testosterone concentrations are due to modification of not only gonadal steroid synthesis but also are due to changes in hepatic degradation of these hormones.
The experimental plan involves the following specific approaches: 1) identify the normal circulating concentration of sex steroid hormones and their metabolites in late embryonic, neonatal, juvenile and adult freshwater yellow belly turtles (Trachemys scripta elegans) and American alligators (Alligator mississippiensis) living in contaminated and non-contaminated lakes. This study will provide baseline data on sexual dimorphic hepatic degradation of steroids in normal control populations and the modifications occurring in contaminated environments; 2) treat developing embryos prior to the critical period for sex determination with naturally occurring steroids (estradiol, testosterone) or steroid hormone antagonists to determine the specific effect of embryonic exposure on the functioning and expression of hepatic enzymes associated with steroid degradation; 3) treat developing embryos prior to the critical period for sex determination with various xenobiotic agents (persistent and modern pesticides and herbicides actively used in the research locality) to determine the effects on gonadal development and hepatic function; 4) determine the chemical identity of the unique hepatic steroid metabolites in the environmentally contaminated and experimentally-treated animals. Once identified, determine their antigenic properties and either purchase or make antibodies useful in the development of an assay (radioimmunoassay or ELISA) procedure to quantify metabolite presence in urine or plasma. Validate the assay and perform field testing to determine its usefulness in identifying animals from contaminated versus control localities.