1 3 Developmental oestrogen exposure differentially modulates IGF-I 4 and TNF-a expression levels in immune organs of Yersinia 5 ruckeri-challenged young adult rainbow trout (Oncorhynchus mykiss) 6 7 8 Michael Wenger a,b Q1 , Natallia Shved a,c , Gülfirde Akgül a,c , Antje Caelers a , Ayako Casanova b , 9 Helmut Segner b,d , Elisabeth Eppler a,d,⇑ 10 a Research Group Neuro-Endocrine-Immune Interactions, Institute of Anatomy, University of Zurich, Zurich, Switzerland 11 b Centre for Fish and Wildlife Health, Institute of Animal Pathology, University of Bern, Bern, Switzerland 12 c Centre for Evolutionary Medicine (ZEM), Institute of Anatomy, University of Zurich, Zurich, Switzerland 13 d Centre for Xenobiotic Risk Research (XERR), Zurich, Switzerland 14 15 17 article info 18 Article history: 19 Available online xxxx 20 Keywords: 21 Bacteria 22 Fish infection 23 Liver 24 Head kidney 25 Spleen 26 IGF-II 27 28 abstract 29 Intensified aquaculture has strong impact on fish health by stress and infectious diseases and has 30 stimulated the interest in the orchestration of cytokines and growth factors, particularly their influence 31 by environmental factors, however, only scarce data are available on the GH/IGF-system, central physio- 32 logical system for development and tissue shaping. Most recently, the capability of the host to cope with 33 tissue damage has been postulated as critical for survival. Thus, the present study assessed the combined 34 impacts of estrogens and bacterial infection on the insulin-like growth factors (IGF) and tumor-necrosis 35 factor (TNF)-a. Juvenile rainbow trout were exposed to 2 different concentrations of 17b-estradiol (E2) 36 and infected with Yersinia ruckeri. Gene expressions of IGF-I, IGF-II and TNF-a were measured in liver, 37 head kidney and spleen and all 4 estrogen receptors (ERa1, ERa2, ERb1 and ERb2) known in rainbow 38 trout were measured in liver. After 5 weeks of E2 treatment, hepatic up-regulation of ERa1 and ERa2, 39 but down-regulation of ERß1 and ERß2 were observed in those groups receiving E2-enriched food. In 40 liver, the results further indicate a suppressive effect of Yersinia-infection regardless of E2-treatment 41 on day 3, but not of E2-treatment on IGF-I whilst TNF-a gene expression was not influenced by 42 Yersinia-infection but was reduced after 5 weeks of E2-treatment. In spleen, the results show a stimula- 43 tory effect of Yersinia-infection, but not of E2-treatment on both, IGF-I and TNF-a gene expressions. In 44 head kidney, E2 strongly suppressed both, IGF-I and TNF-a. To summarise, the treatment effects were 45 tissue- and treatment-specific and point to a relevant role of IGF-I in infection. 46 Ó 2014 Published by Elsevier Inc. 47 48 49 50 1. Introduction 51 A role for the growth hormone (GH)-insulin-like growth factor 52 (IGF) system in immune competence and functionality has been 53 debated for decades in mammals (for review see: Clark, 1997; 54 Weigent, 2013). Both, GH and IGF-I, have been attributed beneficial 55 and restoring effects in immune organ and cell development, dif- 56 ferentiation and recovery, e.g., for murine B cell lineage differentia- 57 tion (Landreth et al., 1992), for shaping and sustaining the human 58 lymph node architecture (Oberlin et al., 2009), and for macrophage 59 functionality in rat, mice and humans (Hansson et al., 1988; Arkins 60 et al., 1993; Kelley and Arkins, 1994). A particular role for the 61 GH/IGF-I axis was found in the recovery of CD4+ T helper cells in 62 HIV-infected individuals treated with GH where beneficial effects 63 coincided with increased IGF-I serum levels (Napolitano et al., 64 2008). Vice versa, lowered IGF-I serum levels were measured in 65 children during sepsis and septic shock (Onenli-Mungan et al., 66 2004) and in non-survivors from septic shock as compared to the 67 survivors (De Groof et al., 2002). Nevertheless, data are very 68 fragmentary still (for further reading see: Oberlin et al., 2009; 69 Weigent, 2013). 70 Intensified aquaculture has strong impact on fish growth and 71 health by stress and infectious diseases and has tremendously 72 stimulated the interest in the complex orchestration of cytokines 73 and growth factors in fish, particularly their influences by 74 environmental factors (Bowden, 2008; Secombes, 2008; Verburg 75 van-Kemenade et al., 2009; Workenhe et al., 2010; Wang and http://dx.doi.org/10.1016/j.ygcen.2014.05.022 0016-6480/Ó 2014 Published by Elsevier Inc. ⇑ Corresponding author. Address: Institute of Neuroradiology, University Hospital, Otto-von-Guericke-University Magdeburg, Germany. Fax: +41 44 63 55 702 Q2 . E-mail address: elisabeth.eppler@uzh.ch (E. Eppler). General and Comparative Endocrinology xxx (2014) xxx–xxx Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen YGCEN 11844 No. of Pages 8, Model 5G 30 May 2014 Please cite this article in press as: Wenger, M., et al. Developmental oestrogen exposure differentially modulates IGF-I and TNF-a expression levels in immune organs of Yersinia ruckeri-challenged young adult rainbow trout (Oncorhynchus mykiss). Gen. Comp. Endocrinol. (2014), http://dx.doi.org/ 10.1016/j.ygcen.2014.05.022