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TP5 Mechanisms of Toxic Action
() The mechanism behind the association of tributyltin exposure with increased testosterone in prosobranch gastropods: insights.
Sternberg, R1, Ranhotra, H1, Gooding, M1, LeBlanc, G1, 1 North Carolina State University, Raleigh, NC, USA
ABSTRACT- Exposure to the marine contaminant tributyltin (TBT) has been casually linked with imposex, the imposition of male secondary sex characteristics on female prosobranch gastropods. Past studies have associated TBT exposure with increased testosterone titers in imposexed females. We previously established that the fatty acid esterification of testosterone by microsomal acyl-CoA:testosterone acyltransferase (ATAT) is a major process for maintaining free testosterone homeostasis in the Eastern mud snail, Ilyanassa obsoleta. This research sought to elucidate the mechanism behind the association of TBT exposure with elevated testosterone concentrations by examining the effects of TBT on ATAT activity. Exposure of snails to TBT reduced the accumulation of testosterone-fatty acid esters by these organisms. However, ATAT activity in microsomes isolated from TBT-exposed snails was not suppressed, nor was microsomal ATAT activity directly inhibited by TBT in vitro. In contrast, exposure of snails to testosterone elevated ATAT activity in microsomal preparations, and prior exposure to TBT significantly attenuated this induction. These results indicate that TBT increases free testosterone levels by preventing the induction of ATAT activity normally associated with elevated free testosterone levels. TBT thus appears to interfere with the positive feedback control of testosterone esterfication.
Key words: tributyltin, imposex, testosterone esterification, Ilyanassa obsoleta
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