Mode of Action of Organotins to Induce the Development of Imposex in Gastropods, Focusing on Steroid and the Retinoid X Receptor Activation Hypotheses

Abstract

Basic knowledge of endocrinology or reproductive physiology of pros-obranch gastropods is reviewed, focusing on vertebrate-type steroids as possible sex hormones in gastropods. Major points of the view for criticism are steroid-producing cells, enzymes to synthesize and/or metabolize steroids, and functional receptors for steroids. Mechanism of induction and promotion of the development of imposex is also reviewed, regarding six hypotheses proposed as the mechanism by which organotins, such as TBT and TPhT, induce the development of imposex in gastropods: (1) an increase in androgen (e.g., testosterone) levels as a result of TBT-mediated inhibition of aromatase; (2) an increase in testosterone levels owing to the inhibition of acyl CoA-steroid acyltransferase; (3) TBT-mediated inhibition of the excretion of androgen sulfate conjugates, with a consequent increase in androgen levels; (4) TBT interference with the release of penis morphogenetic/ retrogressive factor from the pedal/cerebropleural ganglia; (5) an increase in the level of an alanine-proline-glycine-tryptophan amide (APGWamide) neuropeptide in response to TBT; and (6) activation of the retinoid X receptor (RXR). The latest information about nuclear receptors other than RXR in gastropods, namely, retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR), is also described. Keywords Aromatase • Alanine-proline-glycine-tryptophan amide (APGWamide) • Enzymes to synthesize steroids • Functional receptors for steroids • Retinoid X receptor (RXR) • Sex hormones • Steroid-producing cells • Tributyltin (TBT) • Triphenyltin (TPhT) • Vertebrate-type steroids