Biotransformation and disposition of testosterone in the eastern mud snailIlyanassa obsoleta

Elevated testosterone levels have been reported to be associated with impos er (pseudohermaphroditism), the superimposition of male characteristics suc h as a penis and vas deferens on female gonachoristic snails. Tributyltin ( TBT), a marine biocide in anti-fouling paints, is a known causal agent of i mposer. Evidence suggests that imposer is elicited by TBT-mediated changes in the biotransformation and disposition of testosterone. To identify poten tial targets of TBT in gastropod species susceptible to imposer, biotransfo rmation and disposition of testosterone in normal individuals must first be characterized. Nonimposex mud snail, Ilyanassa obsoleta, readily extracted [C-14] testosterone, added to aqueous media, and converted the testosteron e to at least five apolar conjugates designated AP1 through APS. All were r etained by the organisms. No significant amount of [C-14]testosterone was r etained or eliminated as polar metabolites. Following enzymatic hydrolysis of the most abundant metabolite (AP1), free fatty acids and [C-14] testoste rone were liberated. Furthermore, AP1 was produced when homogenized snail t issue was incubated with [C-14]testosterone and oleoyl coenzyme A or palmit oyl coenzyme A. These results indicate that AP1, which represents over 70% of the testosterone biotransformation products, is a fatty acid ester of te stosterone. Apolar metabolites AP2-AP5 might represent testosterone derivat ives that are multiply conjugated to fatty acid molecules. Fatty acid conju gates of testosterone have not been previously described in the gastropods. The esterification of testosterone to fatty acids might be a mechanism whe re by steroid titers are regulated and could represent a target of TBT toxi city. (C) 2001 Academic Press.