PUBLICATION
Interaction of Environmental Steroids with Organic Anion Transporting Polypeptide (Oatp1d1) in Zebrafish (Danio Rerio)
- Authors
- Willi, R.A., Fent, K.
- ID
- ZDB-PUB-180729-2
- Date
- 2018
- Source
- Environmental toxicology and chemistry 37(10): 2670-2676 (Journal)
- Registered Authors
- Keywords
- Endocrine disruption, active transport, steroids, toxicokinetics, transporters, zebrafish Oatp1d1
- MeSH Terms
-
- Zebrafish/metabolism*
- Fluorescence
- Humans
- Inhibitory Concentration 50
- Organic Anion Transporters/metabolism*
- Zebrafish Proteins/metabolism*
- Animals
- Steroids/metabolism*
- PubMed
- 30055005 Full text @ Environ. Toxicol. Chem.
Citation
Willi, R.A., Fent, K. (2018) Interaction of Environmental Steroids with Organic Anion Transporting Polypeptide (Oatp1d1) in Zebrafish (Danio Rerio). Environmental toxicology and chemistry. 37(10):2670-2676.
Abstract
Steroid hormones in the aquatic environment may pose a risk to fish health due to their ubiquitous presence and high biological activity. At present, the uptake process and toxicokinetics of steroids in fish are poorly known, particularly the role of cell membrane transporters. Here we investigated the interaction of 17 endogenous and environmental steroids with zebrafish organic anion uptake transporter Oatp1d1 that is prominently expressed liver and kidneys. We selected steroids of different classes including androstenedione (A4), progesterone (P4) and metabolites, as well as glucocorticoids and spironolactone by competitive inhibition of Lucifer Yellow (LY) uptake. The half-maximal inhibition (IC50 ) values derived from sigmoid inhibition curves were lowest for P4 followed by the following order of increasing IC50 values: 17?-hydroxyprogesterone?>?clobetasol propionate?>?spironolactone?>?21?-hydroxyprogesterone?>?fludrocortisone acetate and additional glucocorticoids. The interaction activity showed a positive correlation with the lipophilicity of the steroids. Our data show that different classes of steroids interact with Oatp1d1 with different activity either by uptake and/or as inhibitors. This is of importance, because in consequence, steroids may interfere with the transport of endogenous substrates, and thus physiological processes. Moreover, steroids may alter cellular trafficking of environmental contaminants by competitive inhibition. This article is protected by copyright. All rights reserved.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping