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THE BIOCIDE TRIBUTYLTIN REDUCES THE RETENTION OF TESTOSTERONE AS FATTY ACID ESTERS IN THE MUD SNAIL (ILYANASSA OBSOLETA)
Gooding, M. P., V S. Wilson, L C. Folmar, D T. Marcovich, AND G. A. LeBlanc. THE BIOCIDE TRIBUTYLTIN REDUCES THE RETENTION OF TESTOSTERONE AS FATTY ACID ESTERS IN THE MUD SNAIL (ILYANASSA OBSOLETA). ENVIRONMENTAL HEALTH PERSPECTIVES 111(4):426-430, (2003).
Imposex, the development of male sex characteristics by female gonochoristic snails, has been causally associated with exposure to the ubiquitous environmental contaminant tributyltin (TBT). Documentation of imposex distribution indicates that this masculinization of marine snails is occurring globally and causes reproductive impairment in some species. Elevated testosterone levels in snails also are associated with TBT and direct exposure to testosterone has been shown to cause imposex. Previously, we had characterized normal testosterone biotransformation in the eastern mud snail (Ilyanassa obsoleta). We discovered that this species converts testosterone primarily to fatty acid esters and that this activity is mediated by an acyl CoA:testosterone acyltransferase (ATAT). The purpose of the present study was to determine whether TBT interferes with the esterification of testosterone resulting in the elevated testosterone levels associated with imposex. Snails were exposed for three to six months to environmentally-relevant concentrations of TBT (0.10, 1.0 and 10 ng/L as Sn). Imposex was marginally induced (10% incidence) at 0.10 ng/L and significantly, 27% and 28% incidence, at 1.0 and 10 ng/L, respectively. Total testosterone levels in snails were not altered by TBT; however, free testosterone levels increased with increasing concentration of TBT. TBT-exposed snails were exposed to [14C]testosterone to measure the rate of production of [14C]testosterone fatty-acid ester. The production of testosterone fatty-acid ester decreased with increasing exposure concentration of TBT. These results indicate that TBT elevates free testosterone levels in snails by decreasing the rate of conversion of free testosterone to fatty acid ester. These findings were confirmed in field-sampled imposexed and non-imposexed snails. Individuals collected from a high tin-impacted site exhibited a greater incidence of imposex, higher free testosterone levels, and, lower testosterone-fatty acid ester levels when compared to individuals sampled from a low tin-impacted site. Additional experiments indicated that decreased testosterone-fatty acid esterification among TBT-treated snails was not due to the direct inhibition of ATAT enzyme by TBT nor to suppressed ATAT protein expression. The target of TBT may be a co-contributor to testosterone fatty esterification process or due to enhanced hydrolysis of the testosterone-fatty acid pool.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
REPRODUCTIVE TOXICOLOGY DIVISION