Ethinylestradiol differentially interferes with IGF-I in liver and extrahepatic sites during development of male and female bony fish

Abstract

Growth and sexual development are closely interlinked in fish; however, no reports exist on potential effects of estrogen on the GH/IGF-I-axis in developing fish. We investigate whether estrogen exposure during early development affects growth and the IGF-I system, both at the systemic and tissue level. Tilapia were fed from 10 to 40 days post fertilization (DPF) with 17a-ethinylestradiol (EE 2 ). At 50, 75, 90, and 165 DPF, length, weight, sex ratio, serum IGF-I (RIA), pituitary GH mRNA and IGF-I, and estrogen receptor a (ERa) mRNA in liver, gonads, brain, and gills (real-time PCR) were determined and the results correlated to those of in situ hybridization for IGF-I. Developmental exposure to EE 2 had persistent effects on sex ratio and growth. Serum IGF-I, hepatic IGF-I mRNA, and the number of IGF-I mRNA-containing hepatocytes were significantly decreased at 75 DPF, while liver ERa mRNA was significantly induced. At 75 DPF, a transient decline of IGF-I mRNA and a largely reduced number of IGF-I mRNA-containing neurons were observed in the female brain. In both sexes, pituitary GH mRNA was significantly suppressed. A transient downregulation of IGF-I mRNA occurred in ovaries (75 DPF) and testes (90 DPF). In agreement, in situ hybridization revealed less IGF-I mRNA signals in granulosa and germ cells. Our results show for the first time that developmental estrogen treatment impairs GH/IGF-I expression in fish, and that the effects persist. These long-lasting effects both seem to be exerted indirectly via inhibition of pituitary GH and directly by suppression of local IGF-I in organ-specific cells.

The Reversible Sex of Gonochoristic Fish: Insights and Consequences

“…data]. Similarly, transient and persistent effects on growth and gene expression have been shown in tilapia following fry exposure to environ-mental factors that induced sex reversal [Shved et al, 2007). They can be used to reveal precocious exposure to environmental cues.…”

Tamoxifen persistently disrupts the humoral adaptive immune response of gilthead seabream (Sparus aurata L.)

“…1) were carried out with mature gilthead seabream males (n ¼ 106), with a body weight of 453 ± 7 g, in 2 m 3 aquaria. Briefly, the EE 2 or Tmx (SigmaeAldrich) were incorporated in the commercial food at 5 or 100 mg/g food, respectively, using the ethanol evaporation method (0.3 l ethanol/kg of food) as described elsewhere (Shved et al, 2007). The specimens were fed ad libitum three times a day with the pellet diet supplemented with EE 2 or Tmx for 50 days.…”

“…Although there are few studies on the effects of estrogens on the fish immune response (Iwanowicz et al, 2009;Milla et al, 2011;Shved et al, 2007) it has been demonstrated that they can affect immune cells and modulate some of their activities, as has been seen in the case of the phagocytic activity of tilapia head kidney leukocytes (Law et al, 2001).…”

Estrogen Signaling through the G Protein–Coupled Estrogen Receptor Regulates Granulocyte Activation in Fish

“…Briefly, G1 was incorporated in the commercial food to give a concentration of 0, 2, and 20 mg/fish/day, using the ethanol evaporation method (0.3l ethanol/kg food), as described elsewhere (44). The specimens were fed three times per day ad libitum with the G1-containing food for up to 50 d and fasted for 24 h before sampling.…”