In vivo effects of 17α-ethinylestradiol, 17β-estradiol and 4-nonylphenol on insulin-like growth-factor binding proteins (igfbps) in Atlantic salmon

Abstract Feminizing endocrine disrupting compounds (EDCs) affect the growth and development of teleost fishes. The major regulator of growth performance, the growth hormone (Gh)/insulin-like growth-factor (Igf) system, is sensitive to estrogenic compounds and mediates certain physiological and potentially behavioral consequences of EDC exposure. Igf binding proteins (Igfbps) are key modulators of Igf activity, but their alteration by EDCs has not been examined. We investigated two life-stages (fry and smolts) of Atlantic salmon ( Salmo salar ), and characterized how the Gh/Igf/Igfbp system responded to waterborne 17α-ethinylestradiol (EE 2 ), 17β-estradiol (E 2 ) and 4-nonylphenol (NP). Fry exposed to EE 2 and NP for 21 days had increased hepatic vitellogenin ( vtg ) mRNA levels while hepatic estrogen receptor α ( erα ), gh receptor (ghr) , igf1 and igf2 mRNA levels were decreased. NP-exposed fry had reduced body mass and total length compared to controls. EE 2 and NP reduced hepatic igfbp1b1 , -2a , -2b1 , -4 , -5b2 and -6b1 , and stimulated igfbp5a . In smolts, hepatic vtg mRNA levels were induced following 4-day exposures to all three EDCs, while erα only responded to EE 2 and E 2 . EDC exposures did not affect body mass or fork length; however, EE 2 diminished plasma Gh and Igf1 levels in parallel with reductions in hepatic ghr and igf1 . In smolts, EE 2 and E 2 diminished hepatic igfbp1b1 , -4 and -6b1 , and stimulated igfbp5a . There were no signs of compromised ionoregulation in smolts, as indicated by unchanged branchial ion pump/transporter mRNA levels. We conclude that hepatic igfbps respond (directly and/or indirectly) to environmental estrogens during two key life-stages of Atlantic salmon, and thus may modulate the growth and development of exposed individuals.