Please use this identifier to cite or link to this item:
http://bura.brunel.ac.uk/handle/2438/19166
Title: | Early embryonic exposure of freshwater gastropods to pharmaceutical 5α-reductase inhibitors results in a surprising open-coiled “banana-shaped” shell |
Authors: | Baynes, A Montagut Pino, G Huong Duong, G Lockyer, AE McDougall, C Jobling, S Routledge, EJ |
Keywords: | 5-alpha-reductase;5α-reductase;DET2;SRD5A;embryogenesis;body patterning;endocrinology |
Issue Date: | 11-Nov-2019 |
Publisher: | Springer Nature |
Citation: | Baynes, A. et al. (2019) 'Early embryonic exposure of freshwater gastropods to pharmaceutical 5α-reductase inhibitors results in a surprising open-coiled “banana-shaped” shell', Scientific Reports, 9, 16439, pp. 1 - 12. doi:10.1038/s41598-019-52850-x |
Abstract: | 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. |
Description: | 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. |
URI: | https://bura.brunel.ac.uk/handle/2438/19166 |
DOI: | https://doi.org/10.1038/s41598-019-52850-x |
Other Identifiers: | ORCID iDs: Alice Baynes https://orcid.org/0000-0002-6337-5956; Anne E. Lockyer https://orcid.org/0000-0002-3498-2423; Susan Jobling https://orcid.org/0000-0002-9322-9597; Edwin J Routledge https://orcid.org/0000-0001-7695-364X. 16439 |
Appears in Collections: | Dept of Life Sciences Research Papers Institute of Environment, Health and Societies |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
FullText.pdf | Copyright © The Author(s) 2019. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. | 1.94 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License