National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), https://www.nc3rs.org.uk/ grant ‘The Snail Assay as an Alternative to the Rodent Hershberger Assay for Detecting Androgens and Anti-androgens’ G0900802/1

Baynes, A

Huong Duong, G

Jobling, S

Lockyer, AE

McDougall, C

Montagut Pino, G

Routledge, EJ

Scientific Reports

Data availability: All data generated or analysed during this study are included in this published article (and its Supplementary Information Files). Data produced during pilot studies linked to this work are available from the corresponding author on reasonable request.Copyright © The Author(s) 2019. In vertebrates, the steroidogenesis enzyme 5α-reductase converts testosterone to the more potent androgen 5α-dihydrotestosterone. Homologues of 5α-reductase genes have been identified in molluscs. However, recent findings suggest that vertebrate-type steroid androgens are not utilised in molluscan reproductive development. Genomic searches have revealed that molluscs do not possess many of the steroidogenic enzymes required to make testosterone, nor a nuclear androgen receptor. Consequently, the role of 5α-reductase in molluscs presents a mystery. Here, developmental exposures of Biomphalaria glabrata to selective pharmaceutical 5α-reductase inhibitors elicited a strong, highly reproducible phenotypic response characterised by the development of elongated “banana-shaped” shell morphology. In comparison to untreated snails, the shells are open-coiled and the whorls are unattached. Dutasteride (5α-reductase inhibitor) is approximately 10-times more potent at provoking the banana-shaped shell phenotype than finasteride, paralleling the pharmaceuticals’ efficacy in humans. Other enzyme inhibitors with different modes of action were tested to investigate the specificity of the phenotype. However, only the pharmaceutical 5α-reductase inhibitors provoked the response. Dutasteride elicited the same phenotype in a second gastropod, Physella acuta. In the absence of evidence for de novo androgen steroidogenesis in molluscs, these findings suggest that novel substrates for 5α-reductase exist in gastropods, lending support to the contention that molluscan endocrinology differs from the well-characterised vertebrate endocrine system.National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), https://www.nc3rs.org.uk/ grant ‘The Snail Assay as an Alternative to the Rodent Hershberger Assay for Detecting Androgens and Anti-androgens’ G0900802/1

Brunel University Research Archive

Early embryonic exposure of freshwater gastropods to pharmaceutical 5α-reductase inhibitors results in a surprising open-coiled “banana-shaped” shell

http://bura.brunel.ac.uk/bitstream/2438/19166/4/FullText.pdf

Early embryonic exposure of freshwater gastropods to pharmaceutical 5α-reductase inhibitors results in a surprising open-coiled “banana-shaped” shell

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