Environmentally Relevant Concentrations of 17α-Ethinylestradiol (EE2) Interfere With the Growth Hormone (GH)/Insulin-Like Growth Factor (IGF)-I System in Developing Bony Fish

Abstract

The aim of this study was to evaluate whether effects of environmental estrogens on fish growth and reproduction may be mediated via modulating the growth hormone (GH)/insulin-like growth factor I (IGF-I) system. To this end, developing male and female monosex populations of tilapia were exposed to 17alpha-ethinylestradiol (EE2) at 5 and 25 ng EE2/l water from 10-day postfertilization (DPF) until 100 DPF. Under exposure to both EE2 concentrations, sex ratio shifted toward more females and body length, and weight were significantly reduced in males. The growth-reducing effect was associated with significant changes in hepatic IGF-I expression, both in males and females and with significant alterations of IGF-I mRNA and GH mRNA in the brain. The changes in IGF-I and GH mRNA were accompanied by altered estrogen receptor alpha (ERalpha) expression in brain and liver. These findings point to an influence of estrogenic exposure on the endocrine GH/IGF-I axis. In addition, the EE2 treatment resulted in significant changes of ERalpha and IGF-I expression in ovaries and testis, suggesting that the estrogens interact not only with the endocrine but also with the autocrine/paracrine part of the IGF-I system. Overall, our results provide evidence that EE2 at environmentally relevant concentrations is able to interfere with the GH/IGF-I system in bony fish and that the impairing effects of estrogens reported on fish growth and reproductive functions may rather result from a cross talk between the sex steroid and the IGF-I system than be toxicological.

Identification and Transcriptional Modulation of the Largemouth Bass, Micropterus salmoides, Vitellogenin Receptor During Oocyte Development by Insulin and Sex Steroids1

“…Crosstalk between ERs and INS-signaling systems has been well accepted by the mammalian communities and, although not as well studied, a few studies support this notion in fish. For example, treatment of tilapia with a strong estrogen 17a-ethinylestradiol (EE 2 ) significantly elevated igf-1 expression after 100 days posthatching, implying estrogens interact with the autocrine/ paracrine part of INS growth factor-driven networks [63]. The upregulation of esr2b and ar transcript levels by the combination of pINS and E 2 or pINS and 11-KT, but not by either agent alone, implies a complex signaling network that involves hormone-and INS-mediated receptors.…”

Long-term estrogen exposure of whitefish Coregonus lavaretus induces intersex but not Lake Thun-typical gonad malformations

“…Increased number of fish with phenotypically female gonads as a result of estrogen exposures during gonad development were also reported in other fish species (e.g. in the Japanese medaka Oryzias latipes, Gray & Metcalfe 1997; in tilapia Oreochromis niloticus, Shved et al 2008; and in the white sucker Catostomus commersonii, Vajda et al 2008). In gonochorists such as whitefish, sex steroids act as organizers of sex differentiation during a sensitive window of gonad development (Yamamoto 1969, Devlin & Nagahama 2002.…”

“…The underlying mechanisms of this growth inhibitory effect of estrogen exposure may be a crosstalk between the estrogen and the growth hormone (GH) / insulin-like growth factor (IGF) systems. Indeed, there exists good evidence that estrogens are able to interfere with both the endocrine GH/IGF-I system, through suppression of GH-dependent IGF-I synthesis in the liver, and with the paracrine IGF-I system, through local IGF production in the gonads , Shved et al 2007, Shved et al 2008. Alternatively, the reduced weight increase may result from reduced energy allocation due to increased demands for E2 metabolism, or it might be indicative of a toxicological effect of the prolonged administration of exogenous E2.…”

Sources, factors, mechanisms and possible solutions to pollutants in marine ecosystems

“…Adverse effects of pharmaceuticals to fish and aquatic life are typically detected in aquatic ecosystems (Grondel et al, 1985;Wishkovsky et al, 1987;Vos et al, 2000;Arukwe, 2001;Jobling et al, 2002Jobling et al, , 2006Cleuvers, 2003Cleuvers, , 2004; Thorpe et al, 2003;Brooks et al, 2003Brooks et al, , 2005Schwaiger et al, 2004;Triebskorn et al, 2004;Hoeger et al, 2005;Flippin et al, 2007;Oaks et al, 2004;Caminada et al, 2006;Cunningham et al, 2006;Fent et al, 2006;Filby et al, 2007;Flippin et al, 2007;Johnston et al, 2007;Kim et al, 2007;Owen et al, 2007;Runnalls et al, 2007;Shved et al, 2008;Christen et al, 2010;Corcoran et al, 2010;Nassef et al, 2010;Santos et al, 2010;Cuthbert et al, 2011). Adverse effects include for instance the production of reactive oxygen species in fish (Gonzalez et al, 1998;Laville et al, 2004;Fent et al, 2006;Mostofa et al, 2013aMostofa et al, , 2013b.…”

“…Among the observed effects, there are: reduction in growth, sperm count, egg production, and reproduction; sexual disruption; inhibition of settlement of larvae; disruption in mitochondrial function, intestine, and immune systems; impaired spermatogenesis; disruption in energy metabolism; cytotoxicity in liver, kidney, and gills; oxidative stress in membrane cells; changes in appetite (Webb, 2001;Jobling et al, 2002Jobling et al, , 2006Cleuvers, 2003Cleuvers, , 2004Thorpe et al, 2003;Schwaiger et al, 2004;Triebskorn et al, 2004;Hoeger et al, 2005;Caminada et al, 2006;Crane et al, 2006;Fent et al, 2006;Filby et al, 2007;Flippin et al, 2007;Johnston et al, 2007;Kim et al, 2007;Owen et al, 2007;Runnalls et al, 2007;Shved et al, 2008;Christen et al, 2010;Corcoran et al, 2010;Nassef et al, 2010;Santos et al, 2010;Cuthbert et al, 2011). As far as ecosystems are concerned, effects may include a decline in biodiversity at different trophic levels such as bacteria, algae, zooplankton, fish, crustaceans, and invertebrates.…”