Modulation of steroidogenesis and estrogen signalling in the estuarine killifish ( Fundulus heteroclitus) exposed to ethinylestradiol

• Published in: Aquatic toxicology 2010-06, Vol.98 (2), p.148-156
• Main Authors: Hogan, Natacha S., Currie, Suzanne, LeBlanc, Sacha, Hewitt, L. Mark, MacLatchy, Deborah L.
• Format: Article
• Language: English
• Subjects: Animal and plant ecology; Animal, plant and microbial ecology; Animals; Applied ecology; Biological and medical sciences; Brackish; Brackish water ecosystems; Colforsin - toxicity; Cytochrome P-450 Enzyme System - blood; Cytochrome P-450 Enzyme System - metabolism; Ecotoxicology, biological effects of pollution; Endocrine disruption; Endocrine Disruptors - blood; Endocrine Disruptors - metabolism; endocrine-disrupting chemicals; estradiol; Estrogen receptor; Estrogen Receptor alpha - blood; Estrogen Receptor alpha - metabolism; Estrogens - blood; Estrogens - metabolism; Ethinyl Estradiol - toxicity; Ethinylestradiol; Female; Fertilization - drug effects; Fertilization - physiology; Freshwater; Fundamental and applied biological sciences. Psychology; Fundulidae - genetics; Fundulidae - physiology; Fundulus heteroclitus; gene expression; General aspects; Heat shock proteins; Heat-Shock Proteins - blood; Heat-Shock Proteins - metabolism; Hydroxycholesterols - toxicity; Liver - drug effects; Liver - metabolism; Male; Marine; Pregnenolone - toxicity; signal transduction; Signal Transduction - drug effects; Steroidogenesis; Steroids - biosynthesis; Synecology; Testosterone - blood; Testosterone - metabolism; Time Factors; Vitellogenin; Vitellogenins - blood; Vitellogenins - metabolism; Water Pollutants, Chemical - toxicity; water pollution
• ISSN: 0166-445X; 1879-1514
• DOI: 10.1016/j.aquatox.2010.02.002

Previous studies have shown that mummichog ( Fundulus heteroclitus; a lunar, asynchronous-spawning killifish of the western Atlantic) exposed to 17α-ethynylestradiol (EE2) exhibit decreased plasma reproductive steroid levels, decreased gonadal steroid production, increased plasma vitellogenin, decreased fecundity and impaired fertilization. The objective of this study was to determine the potential mechanisms by which EE2 depresses gonadal steroidogenesis and influences estrogen signalling in the mummichog. Adult recrudesced fish were exposed to the potent synthetic estrogen, ethinylestradiol (EE2; 0–270 ng/L) for 14 days. Following exposure, gonadal tissue was removed and incubated for 24 h with stimulators of steroidogenesis, including forskolin; 25-OH cholesterol; or pregnenolone. Testosterone production was decreased in basal, forskolin-stimulated and pregnenolone-stimulated EE2-exposed males, indicating effects on the steroidogenic pathway both at and downstream of cholesterol mobilization to P450 side-chain cleavage (P450scc) and/or P450scc conversion of cholesterol to pregnenolone. Hepatic transcript levels of estrogen receptor alpha (ERα) and vitellogenin were increased in EE2-treated males compared to control recrudescing males and females confirming an estrogenic response. Hepatic heat shock protein 90 (Hsp90), a chaperoning molecule involved in estrogen signalling, was not affected by EE2 exposure at either the transcript or protein level. However, higher levels of Hsp90 observed in the membrane fractions of female fish raise interesting questions regarding the influence of gender on Hsp90's role in estrogen signalling. These results demonstrate that EE2 can alter steroid production at specific sites within the steroidogenic pathway and can stimulate hepatic estrogen signalling, providing important information regarding the molecular mechanisms underlying the endocrine response of the mummichog to exogenous estrogen.